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In a search for new anticancer agents with better activity and selectivity, the present work described the synthesis of several new series of sulfachloropyridazine hybrids with thiocarbamates 3a-e, thioureids 4a-h, 5a-e and 4-substituted sulfachloropyridazines 6a, b, 7a, b and 8. The synthesized compounds were screened in vitro against a panel of 60 cancer cell lines in one dose assay. The most potent derivatives 3a, 3c, 4c, 4d, 5e, 7a and 7b were tested for their antiangiogenic activity by measuring their ability to inhibit VEGFR-2. The most potent compounds in VEGFR-2 inhibitory assay were further evaluated for their ability to inhibit PDGFR. In addition, the ability of 4c compound to inhibit cell migration on HUVEC cells and cell cycle effect on UO-31 cells has been studied. The pro-apoptotic effect of compound 4c was studied by the evaluation of caspase-3, Bax and BCl-2. Alternatively, the IC 50 of compounds 3a, 3c, 4c, 5e, 7a and 7b against certain human cancer cell lines were determined. Re-evaluation in combination with γ-radiation was carried out for compounds 4c, 5e and 7b to study the possible synergistic effect on cytotoxicity. Docking studies of the most active compounds were performed to give insights into the binding mode within VEGFR-2 active site., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: New quinazoline benzenesulfonamide hybrids 4a-n were synthesized to determine their cytotoxicity and effect on the miR-34a/MDM4/p53 apoptotic pathway. Materials & methods: Cytotoxicity against hepatic, breast, lung and colon cancer cell lines was estimated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: Compound 4d was the most potent against HepG2 and MCF-7 cancer cells, with potential apoptotic activity verified by a significant upregulation of miR-34a and p53 gene expressions. The apoptotic effect of 4d was further investigated and showed downregulation of miR-21 , VEGF , STAT3 and MDM4 gene expression. Conclusion: The anticancer and apoptotic activities of 4d were enhanced post irradiation by a single dose of 8 Gy γ-radiation. Docking analysis demonstrated a valuable affinity of 4d toward VEGFR2 and MDM4 active sites.

Novel series of aminopyrimidines bearing a biologically active cyclohexenone 3a-f and oxo-selaneylidene moiety 4 , besides selenadiazolopyrimidines ( 5a-e and 7 ), were synthesised using 5,6-diaminouracils as starting materials. Compound 3a exhibited strong anti-proliferative activity against three cell lines: HepG-2 (IC 50 14.31 ± 0.83 µM), A-549 (IC 50 30.74 ± 0.76 µM), and MCF-7 (IC 50 27.14 ± 1.91 µM). Also, it was four times more selectively cytotoxic against WI-38 cell lines than doxorubicin. Furthermore, Topoisomerase II (IC 50 4.48 ± 0.65 µM) and HSP90 (IC 50 1.78 ± 0.11 µM) were both strongly inhibited in vitro by 3a . The cell cycle was halted at the G1-S phase, and total apoptotic cells were 65 times more than control Hep-G2 cells. Besides, it increased caspase-3 gene expression, triggering mitochondrial cell death. Molecular docking study indicated that it could bind to Topoisomerase II and HSP90 binding sites in an inhibitory mode. Its geometric properties were investigated using the density functional theory (DFT). Furthermore, compound 3a demonstrated in silico good oral bioavailability.

Herein, we report the synthesis of a series of new quinazoline sulfonamide conjugates 2-16 and their evaluation as potential anticancer agents via dual targeting of EGFR T790M and VEGFR-2. The newly synthesized compounds were designed based on the structure requirements of the target receptors and were confirmed using spectral data. The compounds were evaluated for their cytotoxicity against four cancer cell lines (HepG2, MCF-7, HCT116 and A549) using MTT assay. The most active compounds were further evaluated for their inhibitory activity against EGFR T790M and VEGFR-2. Compound 15 showed the most significant cytotoxic activity with IC 50  = 0.0977 µM against MCF-7 and the most potent inhibitory activity against both EGFR and VEGFR with IC 50  = 0.0728 and 0.0523 µM, respectively. Compound 15 was able to induce apoptosis in MCF-7 cells and cell cycle arrest at the G2/M phase. The relative safety profile of 15 was assessed using HEK-293 normal cell line and an ADMET profile was carried out. Radiosensitizing evaluation of 15 proved its significant ability to sensitize the cancer cell to the effect of radiation after being subjected to a single dose of 8 Gy gamma irradiation. Molecular docking studies revealed that 15 could bind to the ATP-binding site of EGF and VEGF receptors, inhibiting their activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Targeting CDK4/6 has advanced breast cancer treatment. Herein, new quinazolinones were synthesized with acetamide linkers as potential anti-breast cancer agents. Methods & results: In vitro cytotoxic evaluation on human breast cancer cell lines (MCF7 and MDA-MB-231) identified 1,3-benzodioxole ( 5d ) to be of the highest potency. It showed good inhibitory activity on CDK4/6. Compound 5d arrested the cell cycle at the G1-phase, caused induction of early and late apoptosis in an Annexin V-FITC assay, led to an increase in the level of caspase-3 and upregulated Bax expression and downregulated Bcl-2 in MCF7 cells. Compound 5d showed good radiosensitizing activity when combined with a single dose of 8-Gy γ-radiation. Conclusion: This study introduces quinazolinone scaffolds as new CDK4/6 inhibitors for breast cancer.

Sulfonamides are privileged candidates with potent anti-methicillin-resistant Staphylococcus aureus (MRSA) activity and could replenish the MRSA antibiotic pipeline. The initial screening of a series of quinazolinone benzenesulfonamide derivatives 5-18 against multidrug-resistant bacterial and fungal strains revealed their potent activity. The promising compounds were conjugated with ZnONPs to study the effect of nanoparticle formation on the antimicrobial, cytotoxic and immunomodulatory activity. Compounds 5 , 11 , 16 and 18 revealed promising antimicrobial and cytotoxic activities with superior safety profiles and enhanced activity upon nanoformulation. The immunomodulatory potential of compounds 5 , 11 , 16 and 18 was assessed. Compounds 5 and 11 demonstrated an increase in spleen and thymus weight and boosted the activation of CD4 + and CD8 + T lymphocytes, confirming their promising antimicrobial, cytotoxic and immunomodulatory activity.

A set of novel N-substituted-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide 3-16 were designed and synthesized from 2-mercapto-3-phenylquinazolinone 2. The targeted compounds were screened for their cytotoxic activity against the hepatocellular carcinoma cell line HepG-2. Compounds 8, 9, 10, and 11 with IC 50 values of 1.11, 4.28, 5.70, and 4.69 µM, respectively, showed 5.7- to 28-fold higher activities than the positive control doxorubicin (IC 50 32.02 µM). Furthermore, compounds 8 and 9 were tested for EGFR inhibitory activity and demonstrated IC 50 values of 73.23 and 58.26  µM, respectively, when compared to erlotinib's IC 50 value of 9.79 µM. The most potent compounds, 8 and 9, were subjected to a single dose of 8 Gy of γ-radiation, and their cytotoxic efficacy was found to increase after irradiation, demonstrating the synergistic effect of γ-irradiation. Molecular docking was adopted for the most active compounds to confirm their mode of action., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We synthesised a new series of sulphonamide-bearing quinazolinone derivatives 5-18 and evaluated their in vitro cytotoxicity in various cancer cell lines (A549, HepG-2, LoVo and MCF-7) and in normal human cells (HUVEC). Compounds 6 and 10 exhibited the higher activity against all the cancer cell lines compared with 5-flourourcil as positive control. The ability of the most promising compounds 6 and 10 to induce cell cycle arrest and apoptosis in breast cancer (MCF-7) cells was evaluated by flow cytometry. Reverse transcriptase-polymerase chain reaction and western blotting were used to evaluate the expression of apoptosis-related markers. We found that the 2-tolylthioacetamide derivative 6 and the 3-ethyl phenyl thioacetamide derivative 10 exhibited cytotoxic activity comparable to that of 5-fluorouracil as reference drug in MCF-7 and LoVo colon cancer cells. Cell cycle analysis showed a concentration-dependent accumulation of cells in the sub-G1 phase upon treatment with both compounds. The Annexin V-fluorescein isothiocyanate/propidium iodide assay showed that the compounds 6 and 10 increased the early and late apoptosis cell death modes in a dose-dependent manner. These compounds downregulated the expression of B-cell lymphoma-2 (Bcl-2), while increasing that of p53, Bcl-2-like protein 4, and caspase-7, at the mRNA and protein levels. Molecular docking of compounds 6 and 10 with Bcl-2 predicted them to show moderate - high binding affinity ( 6 : -7.5 kcal/mol, 10 : -7.9 kcal/mol) and interactions with key central substrate cavity residues. Overall, compounds 6 and 10 were found to be promising anticancer and apoptosis-inducing agents.

Many quinazoline derivatives with pharmacological properties, such as anticancer activity, have been synthesized. Fourteen quinazoline derivatives bearing a substituted sulfonamide moiety ( 4a-n ) were previously synthesized and fully characterized. These compounds exerted antiproliferative activity against cell lines derived from solid tumors. Herein, the antileukemic activities of these compounds ( 4a-n ) against two different leukemia cell lines (Jurkat acute T cell and THP-1 acute monocytic) were investigated. Our investigation included examining their activity in vivo in a zebrafish embryo model. Remarkably, compounds 4a and 4d were the most potent in suppressing cell proliferation, with an IC 50 value range of 4-6.5 µM. Flow cytometry analysis indicated that both compounds halted cell progression at the G2/M phase and induced apoptosis in a dose-dependent manner. RT-PCR and Western blot analyses also showed that both compounds effectively induced apoptosis by upregulating the expression of proapoptotic factors while downregulating that of antiapoptotic factors. In vivo animal toxicity assays performed in zebrafish embryos indicated that compound 4d was more toxic than compound 4a , with compound 4d inducing multiple levels of teratogenic phenotypes in zebrafish embryos at a sublethal concentration. Moreover, both compounds perturbed the hematopoiesis process in developing zebrafish embryos. Collectively, our data suggest that compounds 4a and 4d have the potential to be used as antileukemic agents.

Twenty new quinazolinone derivatives bearing a piperonyl moiety were designed and synthesized. The structures of the target compounds were in agreement with the microanalytical and spectral data. Compounds 4-10, 13, 14 and 17-27 were screened for their cytotoxic activity against HepG-2 and MCF-7 cancer cell lines. The target compounds showed IC 50 in the range of 2.46-36.85 µM and 3.87-88.93 µM for HepG-2 and MCF-7, respectively. The promising compounds 7, 19, 26 and 27 were selected to measure their EGFR inhibitory activity. The IC 50 values of the promising compounds were in the range of 146.9-1032.7 nM for EGFR in reference to Erlotinib (IC 50  = 96.6 nM). In further studies on compounds 7, 19, 26 and 27 using HepG-2 cell line, there was significant overexpression of p21 and downregulation of two members of IAPs protein family; Survivin and XIAP, relative to their controls. Annexin V-FITC and caspase-3 analyses have established a significant increase in early apoptosis. Moreover, the four selected compounds have impaired cell proliferation by cell cycle arrest at the G2/M phase compared to their respective control. Considering radiotherapy as the primary treatment for many types of solid tumors, the radiosensitizing abilities of compounds 7, 19, 26 and 27 were measured against HepG-2 and MCF-7 cell lines combined with a single dose of 8 Gy gamma radiation. Measurement of the IC 50 of the promising compounds after irradiation revealed their ability to sensitize the cells to the lethal effect of gamma irradiation (IC 50  = 1.56-4.32 µM and 3.06-5.93 µM for HepG-2 and MCF-7 cells, respectively). Molecular docking was performed to gain insights into the ligand-binding interactions of 7, 19, 26 and 27 inside the EGFR binding sites and revealed their essential interactions, explaining their good activity towards EGFR., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In the present work, we report the design and synthesis of a set of iodinated quinazolinones carrying benzenesulfonamide moiety as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The target compounds showed promising inhibitory activity against the four examined human (h) CA isoforms; I, II, IX and XII. Compounds 4-18 displayed variable inhibition constants, ranging as follows: 7.6-782.8 nM for hCA I, 34.4-412.1 nM for hCA II, 29.1-2225.3 nM for hCA IX and 8.8-429.4 nM for hCA XII. Compound 9, the most potent against the tumor-specific CA IX/CA XII (K I  = 29.1 and 8.8 nM) gives the possibility to evaluate its cytotoxicity and selectivity in vitro against HepG-2, HCT-116 and MCF-7 cancer cell lines. Compound 9 showed significant cytotoxicity against the tumor cell lines (IC 50  = 1.78, 1.94 and 3.07 μM, respectively) and relatively lower toxicity against WI38 normal cell line. The radiosensitizing activity of compound 9 was evaluated and displayed an increase in the radiation-induced cell death in cancer cells after receiving a single dose of 8 Gy gamma radiation. Thus, radiation was able to enhance the antiproliferative activity of compound 9. Molecular docking of 9 into the active site of CA IX and XII revealed the key interactions that could explain its potent activity and selectivity towards these isoforms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Multitargeted therapy is considered a successful approach to cancer treatment. The development of small molecule multikinase inhibitors through hybridization strategy can provide highly potent and selective anticancer agents. A library of N-alkyl-2-[(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydroquinazolin-2-yl)thio]acetamide derivatives 5-18 was designed and synthesized. The synthesized compounds were screened for cytotoxic activity against MDA-MB-231 breast cancer cell line and showed IC 50 in the range of 0.34-149.10 µM. The inhibition percentage of VEGFR-2 was measured for all the compounds and found to be in the range of 90.09-20.44%. The promising compounds 8, 12, 13, 16 and 17 were selected to measure their possible multikinase inhibitory activity against VEGFR-2 and EGFR. IC 50 of the promising compounds were in the range of 247-793 nM for VEGFR-2 in reference to sunitinib (IC 50 320 nM), and 369-725 nM for EGFR in reference to erlotinib (IC 50 568 nM). Compounds 12 and 13 showed the most potent activity towards VEGFR-2 & EGFR, respectively. Measuring the cytotoxicity of 12 and 13 against MCF-10 normal breast cell line indicates their relative safety to normal breast cells (IC 50 37 & 97 µM, respectively). As radiotherapy is considered the primary treatment for some types of solid tumors, the radiosensitizing ability of 12 and 13 was measured by subjecting the MDA-MB-231 cells to a single dose of 8 Gy of gamma radiation. IC 50 of 12 and 13 decreased from 1.91 & 0.51 µM to 0.79 & 0.43 µM, respectively. Molecular docking was performed to gain insights into the ligand-binding interactions of 12 inside VEGFR-2 and EGFR binding sites in comparison to their co-crystallized ligands., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Targeting EGFR has proven to be beneficial in the treatment of several types of solid tumours. So, a series of novel 2-(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g]quinazolin-2-ylthio)-N-substituted acetamide 5-19 were synthesised from the starting material 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4H)-yl) benzenesulfonamide 4, to be evaluated as dual EGFR/HER2 inhibitors. The target compounds 5-19, were screened for their cytotoxic activity against A549 lung cancer cell line. The percentage inhibition of EGFR enzyme was measured and compared with erlotinib as the reference drug. Compounds 6, 8, 10, and 16 showed excellent EGFR inhibitory activity and were further selected for screening as dual EGFR/HER2 inhibitors. The four selected compounds showed IC 50 ranging from 0.009 to 0.026 µM for EGFR and 0.021 to 0.069 µM for the HER2 enzyme. Compound 8 was found to be the most potent in this study with IC 50 0.009 and 0.021 µM for EGFR and HER2, respectively.

Two series of 2-aminopyridine derivatives 6-17 and tyrphostin AG17 analogs 18-22 bearing 4-methylbenzenesulfonamide moiety were designed and synthesized as anticancer compounds. The synthesized compounds were biologically evaluated for their cytotoxic activity against human breast cancer cell line MCF-7. From 2-aminopyridine and tyrphostin AG17 series, compounds 14, 16 and 20 showed the best activities with IC 50 values of 20.4, 18.3 and 26.3 µM, respectively compared to E7070 IC 50 36.3 µM. Further biological evaluation of 14, 16 and 20 against cyclin dependent kinase-2 (CDK2) revealed good inhibitory activity with IC 50 of 2.53, 1.79 and 2.92 µM, respectively compared to roscovitine IC 50 0.43 µM. Additionally, capability of γ-radiation to augment the cytotoxic activity of 14, 16 and 20 was studied and showed a dramatic increase in the cell killing effect at lower concentrations after irradiation. Docking was used to investigate the possible binding modes of compounds 14, 16 and 20 inside the active site of CDK2 enzyme., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Dual targeting of EGFR and HER2 is a proven anticancer strategy for the treatment of solid tumors. An array of new N-substituted-2-(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g]quinazolin-2-ylthio) acetamides 5-18 were designed and synthesized from the starting compound 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4H)-yl) benzenesulfonamide 4. The targeted compounds were screened for their cytotoxic activity against MDA-MB-231 breast cancer cell line. The IC 50 of all the compounds were in the range of 0.36-40.90 µM. The percentage inhibition towards EGFR was measured and found to be in the range of 63.00-16.90 %. The most potent compounds 5, 9, 15, 17 and 18 were further screened for their activity against both EGFR and HER2 receptors. The compounds showed IC 50 in the range of 0.64-1.81 µM for EGFR and 1.13-2.21 µM for HER2, in comparison to erlotinib, the reference drug. Compound 17, the most potent towards EGFR in this series, undergoes cell cycle analysis and was found to arrest the cycle at the G2/M phase. Measurement of the cytotoxicity of compound 17 against normal breast cell line showed mild cytotoxic activity. The most potent compounds were subjected to a single dose of 8 Gy of γ-radiation and the cytotoxicity of the tested compounds was found to increase after irradiation, thus proving the synergistic effect of γ-irradiation. Molecular docking was adopted for all the synthesized compounds to confirm their mechanism of action., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In this study, novel series of thioureido-benzenesulfonamide derivatives bearing an enaminone linker either meta or para oriented and having terminal linear or substituted aromatic or heteroaromatic ring system 5-16a,b were designed and synthesized based on the general pharmacophoric features of type II VEGFR2 inhibitors. Evaluation of the synthesized compounds against HEPG2 hepatocellular carcinoma cells in vitro identified compounds 5b, 6b and 10-13b as most active anticancer agents with IC 50 equal to 0.12, 0.29, 0.58, 0.44, 0.42 and 0.66 µM, respectively. These compounds were evaluated for their ability to in vitro inhibit VEGFR2 kinase enzyme. The results demonstrated highly potent dose-related VEGFR2 inhibition with IC 50 values in nanomolar range (33, 57, 210, 37, 37 and 220 nM, respectively). The radiosensitizing ability of the most promising compounds was studied which showed an increase in the cell killing effect of radiation after combination with the synthesized compounds which revealed lowered IC 50 by nearly 50%. Molecular docking for the most potent compounds was performed to predict their possible binding mode within VEGFR2 active site and they showed binding affinity in a similar way to sorafenib., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

An array of some new N-(substituted)-2-((4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g]quinazolin-2-yl)thio)acetamide 5-19 were synthesized from the starting compound 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4H)-yl)benzenesulfonamide 4, to be assessed for their cytotoxic activity against A549 lung cancer cell line and to determine their inhibitory effect on EGFR tyrosine kinase enzyme. Compounds 5-19 showed high activity towards A549 cell line with IC 50 values of 0.12-8.70 μM. Compounds 6, 12 and 18 were the most potent in this series. These compounds were further screened as dual inhibitors for EGFR/HER2 enzymes in comparison with erlotinib and were found to possess very potent activity. Compound 12 showed the highest activity with IC 50 values of 0.06 μM and 0.30 μM towards EGFR and HER2, respectively. Accordingly, the apoptotic effect of the most potent compounds 6, 12 and 18 was investigated and showed a marked increase in the level of caspases-3 by 6, 9 and 8 folds, respectively, compared to the control cells. Moreover, Molecular modeling was performed inside the active site of EGFR, keeping in mind their binding possibilities, bond lengths, angles and energy scores. It was found that the most active compounds demonstrated the best binding scores in the active site of EGFR, which may clarify their high inhibition profile., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Hybrid molecules are used as anticancer agents to improve effectiveness and diminish drug resistance. So, the current study aimed to introduce twenty novel phenothiazine sulfonamide hybrids 5-22, 24 and 25 of promising anticancer activity. Compounds 11 and 13 revealed more potent anticancer properties (IC 50 8.1 and 8.8 μM) than that of the reference drug (doxorubicin, IC 50 = 9.8 μM) against human breast cancer cell line (T47D). To determine the mechanism of their anticancer activity, compounds 5, 6, 7, 11, 13, 14, 16, 17, 19 and 22 that showed promising activity on T47D, were evaluated for their aromatase inhibitory effect. The study results disclose that the most potent aromatase inhibitors 11 and 13 showed the lowest IC 50 (5.67 μM and 6.7 μM), respectively on the target enzyme. Accordingly, the apoptotic effect of the most potent compound 11 was extensively investigated and showed a marked increase in Bax level up to 55,000 folds, and down-regulation in Bcl2 to 5.24*10 -4 folds, in comparison to the control. Furthermore, the effect of compound 11 on caspases 3, 8 and 9 was evaluated and was found to increase their levels by 20, 34, and 8.9 folds, respectively, which indicates the activation of both intrinsic and extrinsic pathways. Also, the effect of compound 11 on the cell cycle and its cytotoxic effect were examined. Moreover, a molecular docking and computer aided ADMET studies were adopted to confirm their mechanism of action., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Thiourea derivatives bearing sulfonamide moiety are well known for their anticancer activity., Objective: The anticancer activity of the target compounds was studied, via inhibition of COX-2 enzyme., Method: A series of novel thioureas 5a-n, 8, quinazoline 6, benzo[g]quinazoline 7 and benzo[1,3] dioxole 10, bearing a sulfonamide moiety was synthesized from the starting compound N-(2,6-dimethoxypyrimidin-4-yl)-4- isothiocyanatobenzenesulfonamide 2. The target compounds were screened against HepG2, MCF-7, Caco-2, HCT-116, PC-3 cancer cell lines and VERO-B normal cell line., Results: Out of all the tested compounds, compound 5c showed a broad selective cytotoxicity against HepG2, MCF-7, Caco-2 and PC-3 cancer cells. Moreover, a sensitization assay was performed on Caco-2 cells, and compound 5c proved to act as a chemosensitizer for cisplatin on colon cancer (Caco-2) cells. The target compounds were further screened in vitro for their anti COX1/COX2 activity and investigated in vivo as antiinflammatory agents against carrageenan-induced rat paw oedema model., Conclusion: Compound 5g showed the most selective inhibitory activity against COX-2. While, compounds 5a, 6, 5m, 5n, 5g and 5i revealed significant anti-inflammatory effect as presented in carrageenan-induced oedema assay. Molecular docking of the tested compounds disclosed important binding modes which may be responsible for their anticancer activity via inhibition of the COX-2 enzyme., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

A series of novel heterocyclic thioureas 3a-u containing sulfonamide moiety have been synthesized by the condensation of isothiocyanatobenzenesulfonamide 2 with a variety of heterocyclic amines. The newly synthesized heterocyclic thioureas were investigated for their antimicrobial and anticancer activity. The in vitro antibacterial and antifungal activity were done using well diffusion method. Interestingly, compounds 3j and 3m, showed similar or better activity compared with the reference drug against the tested microorganisms. Although, 3j was less active among its analogues to inhibit the breast carcinoma cells, it exhibit strong broad spectrum antimicrobial activities. However, The results of the cytotoxic activity revealed that compound 3p was the most active against the breast carcinoma cell line (MCF-7) giving promising IC 50 value of 1.72 μg/mL, compared with reference drug (5-flourouracil) with IC 50 value of 4.8 μg/mL. The most potent compounds in cytotoxic activity 3b and 3p were further docked inside the active site of CAIX and were found to exhibit a proper binding with the active site amino acids according to their bond lengths, angles and conformational energy., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Thirteen novel 1, 2, 4-triazoles incorporating a biologically active sulfonamide moieties 1-13 were designed and synthesized. The structures of the prepared compounds were elucidated on the basis of elemental analyses, IR, 'H-NMR, "C-NMR and mass spectral data. All the newly synthesized compounds were evaluated for their in vino anticancer activity against various cancer cell lines. The corresponding triazole carrying a biologically active free sulfonamide with unsubstituted phenyl ring 1 and triazole bearing sulfonamide with dimethylpyrimidine 11 were the most potent in this study which showed higher activity than the reference drug 2',7'-dichlorofluorescein (DCF). Cytotoxic screening of the tested compounds could offer an encouraging framework in the field that may lead to the discovery of potent anticancer activity.

A novel series of sulfonamide derivatives 4-21 have been synthesized starting from the strategic starting material (E)-4-Chloro-N-(4-(1-(2-(2-cyanoacetyl)hydrazono)ethyl)phenyl) benzenesulfonamide 4. Two series of hydrazone 5-9, and pyridone 10-21 derivatives bearing a sulfonamide moiety were obtained. All the newly synthesized compounds were evaluated for their in vitro cytotoxic activity against human liver cancer cell line (HepG2). Compounds 4-6, 8, 9, 10-14 and 16-18 showed higher activity compared to doxorubicin as a positive control. The radiosensitizing ability of the most promising compounds 4, 10 and 12 was studied which showed an increase in the cell killing effect of γ-radiation after combination with these derivatives. The molecular design was performed to predict the binding mode of the most promising compounds 4, 10 and 12 with the active site of hCA IX, that showed appropriate fitting with the relevant amino acids in the binding pocket on the basis of standard bond lengths, angles, S score and E conformation data., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

As a part of ongoing studies in developing new anticancer agents, novel 1,2-dihydropyridine 4, thienopyridine 5, isoquinolines 6-20, acrylamide 21, thiazolidine 22, thiazoles 23-29 and thiophenes 33-35 bearing a biologically active quinoline nucleus were synthesized. The structure of newly synthesized compounds was confirmed on the basis of elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. 2,3-Dihydrothiazole-5-carboxamides 27, 25, 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (34), 1,2-dihydroisoquinoline-7-carbonitrile (7), 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (35), 1,2-dihydroisoquinoline-7-carbonitrile (6), 2-cyano-3-(dimethylamino)-N-(quinolin-3-yl)acrylamide (21), 1,2-dihydroisoquinoline-7-carbonitriles (11) and (8) exhibited higher activity (IC50 values of 27-45 μmol L-1) compared to doxorubicin (IC50 47.9 μmol L-1). LQ quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (12), 2-thioxo-2,3-dihydrothiazole-5-carboxamide (28) and quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (15) show activity comparable to doxorubicin, while (quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (9), 2,3-dihydrothiazole-5-carboxamide (24), thieno [3,4-c] pyridine-4(5H)-one (5), cyclopenta[b]thiophene-3-carboxamide (33) and (quinolin-3-yl)-6-stryl-1,2-dihydroisoquinoline-7-carbonitrile (10) exhibited moderate activity, lower than doxorubicin.

A novel series of sulfonamide derivatives (14 compounds) bearing thiourea moieties were efficiently synthesized and evaluated for their possible in vitro anticancer activity against four human tumor cell lines. The results indicated that compound 6 was the most potent, showing effectiveness on all the tested cell lines. Compounds 7 and 10 also showed promising results.

By combining the structural features of quinazoline and sulfonamides, novel hybrid compounds 2-21 were synthesized using a simple and convenient method. Evaluation of these compounds against different cell lines identified compounds 7 and 17 as most active anticancer agents as they showed effectiveness on the four tested cell lines. The anticancer screening results of the tested compounds provides an encouraging framework that could lead to the development of potent new anticancer agents.

Background: Quinazoline and sulfonamide derivatives are considered to be important classes of drugs due to their wide range of biological activities especially anticancer., Methods: A novel series of sulfonamides incorporating benzo[g] quinazolinemoieties 2-19 and sulfonyl containing benzo[g] quinazolinemoieties 20, 21 were designed and synthesized starting from 4- chlorobenzo[g] quinazoline 1. In-vitro screening as anticancer agents was done for the synthesized compounds. Molecular docking study was also performed to explore the binding interactions of the synthesized compounds within the active site of carbonic anhydrase IX (CA IX), which most commonly expressed in some types of cancer cells., Conclusion: The results indicated that the most potent compounds were 2 and 7 showing effectiveness on more than one cell line.

Novel sulfonamides 3-19 with a biologically active 3,4-dimethoxyphenyl moiety were designed and synthesized. The structures of the synthesized compounds were established using elemental analyses, IR, 1 H-NMR, 13 C-NMR spectral data and mass spectroscopy. All the synthesized compounds were evaluated for their in vitro anticancer activity against four cancer cell lines, namely human hepatocellular carcinoma (HepG2), human medulloblastoma (Daoy), human cervical cancer (HeLa), and human colon cancer (HT-29), by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and dasatinib as the reference drug. Among the tested derivatives, compounds 4, 10, 16, and 19 showed good activity as cytotoxic agents. The most active derivatives were evaluated for their ability to inhibit vascular endothelial growth factor receptor (VEGFR)-2. Compounds Z-4-(3-(3,4-dimethoxyphenyl)-3-oxoprop-1-enylamino)-N-(5-methyl-1,3,4-thiadiazol-2-yl)-benzenesulfonamide 10 and Z-4-(3-(3,4-dimethoxyphenyl)-3-oxoprop-1-enylamino)-N-(1H-indazol-6-yl)-benzenesulfonamide 19 were more active as VEGFR-2 inhibitors than dasatinib. Molecular docking of the most active derivatives on the active site of VEGFR-2 revealed that compound 19 exhibited favorable and promising results.

A novel series of quinazoline derivatives 2-8, 10-12 were designed and synthesized. Structures of the newly synthesized compounds were confirmed by elemental analyses, IR, 1H and 13C NMR spectral data. All the newly synthesized compounds were evaluated for in vitro cytotoxic activity against the breast cancer cell line MCF-7. Seven of the novel compounds exhibited higher activity than the reference drug doxorubicin. The corresponding compounds 3, 4, 5, 8, 10, 11 and 12 exhibited higher activity with IC50 values from 22.75 to 43.44 μmol L-1, compared to the reference drug doxorubicin with IC50 value of 47.90 μmol L-1. Also, compounds 1, 6, and 9 are nearly as active as doxorubicin with IC50 values of 48.31, 48.90, and 48.91 μmol L-1, respectively, while compounds 2 and 7 exhibited a moderate activity with IC50 values of 50.44 and 52.37 μmol L-1. In addition, compound 13 showed no activity. Cytotoxic screening of the tested compounds offered an encouraging framework that may lead to the discovery of potent anti-breast cancer activity.

To discover new bioactive lead compounds for medicinal purposes, 2-cyano-3-(4-substituted)-N-(quinolin-3-yl) acrylamide derivatives 2-24, chromenes 25, 26 and benzochromenes 27, 28 were synthesized. The structures of the newly synthesized compounds were confirmed by elemental analyses, IR, 1H NMR and 13C NMR spectroscopies. In addition, the structure of compound 1 was confirmed through X-ray crystallography. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. The corresponding 2-cyano-3-(4-hydroxy-3-methoxyphenyl)-N-(quinolin-3-yl) acrylamide (15), 3-oxo-N-(quinolin-3-yl)-3H-benzol[f] chromene-2-carboxamide (27), 2-cyano-3-(4-fluorophenyl-N-(quinolin-3-yl) acrylamide (7), 2-cyano-5-(4-(dimethyl-amino) phenyl)-N-(quinolin-3-yl) penta-2,4-dienamide (19) exhibited higher activity compared to doxorubicin (with IC50 value of 47.9 μmol L-1) as a reference drug, with IC50 values of 29.8, 39.0, 40.0, 40.4 μmol L-1, resp. Also, quinoline acrylamides containing 2,3,4-trimethoxyphenyl 17, 2-chlorophenyl 10, benzo[d][1,3]dioxol 12, 2-methoxynaphthalen 22, 2,4-dichlorophenyl 18 and quinoline carrying a chromene-3-carboxamide moiety 25 were nearly as active as doxorubicin, while quinoline acrylamides incorporating unsubstituted phenyl 2, p-tolyl 3, 2,4-dienamide 8, 3-nitrophenyl 13, 4-nitrophenyl 14, 3,4-dimethoxyphenyl 16 and chromene 26 exhibited a moderate activity. In addition, quinoline with acetamide 1, 4-hydroxyphenyl 4, 4-dimethylaminophenyl 9, 4-chlorophenyl 11, 3-bromophenyl 20, 4-bromophenyl 21 and 3-thienyl moiety 24 showed less activity than doxorubicin. On the other hand, quinoline having 2-methoxyphenyl 5, 4-methoxyphenyl 6, 4-metho xynaphthalene 23 and chromene-2-carboxamide 28 showed no activity.

In this study, novel series of sulfonamide derivatives were synthesized starting from 2-cyanoacetyl)hydrazono)ethyl)phenyl)benzenesulfonamide 4a and 2-cyanoacetyl)hydrazono)ethyl)phenyl)-4-methylbenzenesulfonamide 4b. Different biologically active moieties as pyrazol, thiophene, pyridine and pyrimidines were introduced in order to investigate their in-vitro anticancer activity, in addition to a novel series of sulfonamide chalcones were synthesized from the reported 4-acetyl-N-(P-tolyl) benzenesulfonamide 3b. The newly synthesized sulfonamide derivatives were characterized by FT-IR, (1)H NMR, (13)C NMR, mass spectroscopy and elemental analyses and were tested for their in-vitro anticancer activity against human tumor liver cell line (HEPG-2). The most potent compounds in this study were compounds 4a, 4b, 5a, 6a, 6b, 8, 9, 11, 13, 18 and 19 which showed higher activity than doxorubicin with IC50 ranging from 11.0 to 31.8 μM. Additionally, eight compounds among the most potent were evaluated for their ability to enhance the cell killing effect of γ-radiation., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

A new series of pyrroles 5, 6, pyrrolopyrimidines 8, 11-14, 16-29, triazolo-pyrrolopyrimidines 9, 10 and 15 carrying a biologically active sulfonamide moities were synthesized using 2-amino-3-cyano-4-(4-bromophenyl)pyrrole 5 as a strategic starting material. The structures of the prepared compounds were confirmed by elemental analyses, IR, 1H-NMR and 13C-NMR data. All of the synthesized compounds showed promising anticancer activity against breast cancer cell line (MCF7) compared to doxorubicin as reference drug, especially compounds 5-17, 21-24 and 28 with better IC50 than that of doxorubicin. In order to suggest the mechanism of action of their cytotoxic activities, molecular docking on the active site of c-Src was done and good results were obtained.

The versatile synthons 2-chloro-N-(4-sulfamoylphenyl)acetamides la,b were used as a key intermediates for the synthesis of sulfonamide derivatives with adamantyl 2, indene 3, morpholinophenyl 4, pipronyl 5, benzothiazole 6-8, pyrazole 9, thiadiazole 10,11, quinoline 12, isoquinoline 13, thiazoles 14-19, acrylamides 20-24 and benzochromene 25 moieties via reaction with several nitrogen nucleophiles. The newly synthesized compounds were screened in vitro for their anticancer activity against breast cancer (MDA-MB-231) and colon cancer (HT-29) cell lines. Compound 17 was found to be the most potent against breast cancer cell lines with IC55 value 66.6 μM compared with the reference drug 5-fluorouracil with IC50 value 77.28 μM.

A novel series of thiophenes having biologically active sulfonamide 2-11, 3-methylisoxazole 12, 4-methoxybenzo[d] thiazole 13, quinoline 14, 15, benzoylphenylamino 16, and anthracene-9,10-dione 17 moieties were prepared. Structures of the newly synthesized compounds were established by elemental analysis and spectral data. All newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Most of the screened compounds showed cytotoxic activities compared to doxorubicin as a positive control. Compounds 6, 7, 9 and 13 (IC50 values 10.25, 9.70, 9.55 and 9.39 μmol L-1) revealed higher cytotoxic activities than that of doxorubicin (IC50 = 32.00 μmol L-1). Also, compounds 5, 8 and 10 were found nearly as active as doxorubicin (IC50 28.85, 23.48 and 27.51 μmol L-1).

Novel pyridine, thiophene, thiazole, chromene and benzochromene derivatives bearing a N,N-dimethylbenzenesulfonamide moiety 6-20 were synthesized. The target compounds were obtained through employing a series of heterocyclization reactions utilizing the key intermediate hydrazide hydrazone derivative 3. The structures of the newly synthesized compounds were confirmed by elemental analyses, IR, (1)H-NMR and (13)C-NMR spectral data. All the newly synthesized compounds were evaluated for their in vitro antiproliferative activity against the human breast cancer cell line MCF-7. Biological screening results showed that sulfonamides 6, 9, 11, 16 and 17 with IC50 values 21.81, 25.50, 20.60, 25.83 and 31.20 μM, respectively, possessed higher antiproliferative activity compared to doxorubicin, IC50 value 32.00 μM, as position control. Molecular docking study was also performed to assess the binding mode of the synthesized sulfonamides with their potential biomolecular target, carbonic anhydrase IX (CA IX), which is usually highly expressed in some types of cancer cells.

Novel nineteen compounds based on a 4-aminoquinoline scaffold were designed and synthesized as potential antiproliferative agents. The new compounds were N-substituted at the 4-position by aryl or heteroaryl (1-9), quinolin- 3-yl (10), 2-methylquinolin-3-yl (11), thiazol-2-yl (12), and dapsone moieties (13, 14 and 18). Bis-compounds 15, 16 and 19 were also synthesized to assess their biological activity. All the newly synthesized comounds were tested for in vitro antiproliferative activity against the MCF-7 breast cancer cell line. Seventeen of the novel compounds showed higher activity than the reference drug doxorubicin. The corresponding 7-(trifluoromethyl)-N-(3,4,5-trimethoxyphenyl)quinolin-4- amine 1, N-(7-(trifluoromethyl)quinolin-4-yl)quinolin- 3- amine (10), 2-methyl-N-(7-trifluorome-thyl)quinolin-4-yl) quinolin-3-amine (11) and N-(4-(4-aminophenylsulfonyl) phenyl)-7-chloroquinolin-4-amine (13) were almost twice to thrice as potent as doxorubicin. Biological screening of the tested compounds could offer an encouraging framework in this field that may lead to the discovery of potent anticancer agents.

The natural alkaloid 1-norephedrine 1 was utlized in the synthesis of some novel thiourea derivatives 2, 5 and thiazolidinones 4a,b and 6, 7. Structures of the synthesized compounds were confirmed by analytical and spectral data. The synthesized compounds were evaluated in vitro for anticancer activity against the human breast (MCF-7), human liver (HEPG2) and human colon (HCT116) cancer cell lines. Thiazolidinone derivative 7 was the most active against all the cell lines with values IC50 = 2.60, 2.80 and 2.60 microg/mL compared with doxorubicin (IC50 = 5.40, 2.97 and 5.26 microg/mL). Thiazolidinone derivative 6 exhibited higher activity with IC50 value (3.20 microg/mL) against HCT116 when compared with doxorubicin with IC50 value (5.26 microg/mL) as positive control.

Abstract: A novel series of pyrroles and pyrrolopyrimdines carrying a biologically active sulfonamide moiety have been synthesized. The structures were confirmed by elemental analyses and spectral data. All the target compounds were subjected to in vitro cytotoxic screening on breast cancer cell line (MCF-7). Most of the synthesized compounds showed good activity as cytotoxic agents with better IC50 than doxorubicin as a reference drug. In order to suggest a mechanism of action for their activity, molecular docking on the active site of human c-Src was performed for all synthesized compounds.

A novel series of newly synthesized thiophene derivatives, ethyl-4,5-dimethyl-2-(3-(3,4,5-trimethoxyphenyl)thioureido)thiophene-3-carboxylate 3, ethyl-2-[(2-(dimethylamino)ethoxy)mercapto)methyleneamino)]-4,5-dimethyl-thiophene-3-carboxylate 9, thienopyrimidines 4, 7, 10-20, triazolothienopyrimidines 5, 6 were prepared and tested for their antiproliferative activity. The structures of the synthesized compounds were confirmed on the basis of elemental analysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data. The results showed that the synthesized compounds were more active on breast cancer than on colon cancer cell lines and the most potent compounds in this study are compounds 3 and 13 which exerted remarkable activity against MDA-MB-231 (breast cancer) and HT-29 (colon cancer) cell lines with IC50 values (40.68, 49.22 μM) for compound 3 and (34.04, 45.62 μM) for compound 13. Also, compounds 4-6, 9 showed a moderate activity against breast cancer cell line, while compounds 15, 19 and 20 showed no activity., (© Georg Thieme Verlag KG Stuttgart · New York.)

4-Aminoantipyrine was utilized as key intermediate for the synthesis of pyrazolone derivatives bearing biologically active moieties. The newly synthesized compounds were characterized by IR, 1H- and 13C-NMR spectral and microanalytical studies. The compounds were screened as anticancer agents against a human tumor breast cancer cell line MCF7, and the results showed that (Z)-4-((3-amino-5-imino-1-phenyl-1H-pyrazol-4(5H)-ylidene)methylamino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 5, 3-(4-bromophenyl) -1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 13, 1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-3-(4-iodophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 14, 3,3'-(4,4'-sulfonylbis(4,1-phenylene))bis(1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile) 16, (Z)-1- (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-hydrazono-4-oxo-3-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 17, (Z)-1-(1,5-dimethyl-3-oxo-2-phenyl- 2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-3-phenyl-2-(2-phenylhydrazono)-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile 18, and (Z)-4-(3-amino-6-hydrazono-7-phenyl-6,7-dihydro pyrazolo[3,4-d]pyrimidin-5-yl)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 19 were the most active compounds with IC50 values ranging from 30.68 to 60.72 µM compared with Doxorubicin as positive control with the IC50 value 71.8 µM.

To discover new bioactive lead compounds for medicinal purposes, herein, (E)-3-(substituted amino)-1-thiophen-2-yl-prop-2-en-1-ones 3-8, aminopyridines 9-11, benzylamine 12, nicotinamide 13, pyrimidines 14, 15, hexanoic acid 16 and triazolopyrimidine 19 were prepared and tested for cytotoxic activity. Results showed that the tested compounds exhibited a remarkable activity, especially compounds 3 and 19 with IC50 values (55.2 and 50.49 microM, respectively) compared to doxorubicin (IC50 = 71.8 microM) as a reference drug.

A series of 4-(substituted)-N-(guanidinyl)benzenesulfonamides bearing biologically active pyrazole, pyrimidine and pyridine moieties were prepared and evaluated for their anticancer activity against human tumor breast cell line (MCF7). These sulfonamides showed promising activity with IC50 values ranging from 49.5 to 70.2 μM. The structure-activity relationship of the synthesized compounds was studied. Interestingly, it was found that the most potent compounds in this study were the corresponding 2-cyanoacrylate 3, 3-oxobutanoate 4, pyrazole 6, pyridine 9 and pyrazole 13. Compounds 7 and 8 are nearly as active as Doxorubicin as reference drug with (IC50 values=70.2, 68.1 μM), while compounds 5, 10 and 11 exhibited a moderate activity.

Several trifluoromethylquinoline derivatives containing a biologically active benzenesulfonamide moiety 2-14, 16, urea derivatives 15, 17, 4-isothiocyanate 18 and the corresponding carbamimidothioic acid derivatives 19-30, were synthesized from the strategic starting material 4-chloro-7-trifluoromethylquinoline 1. The structures of the newly synthesized compounds were elucidated on the basis of elemental and spectral analyses. All the prepared compounds were evaluated for their in vitro anticancer activity against various cancer cell lines. Most of the synthesized compounds showed good activity, especially compound 15 which exhibited higher activity than the reference drug doxorubicin. In order to suggest the mechanism of action for their cytotoxic activity, molecular docking for all synthesized compounds was done on the active site of PI3K and good results were obtained., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

A variety of thiophene derivatives bearing diphenylsulfone 3,4, diazepines 5b, 6b, phenylamino 7, piperidine 8, benzylpiperidine 9, oxazepines 10b, 11b, acrylaldehydes 12-14 and benzeonesulfanamide 15 were synthesized. some newly synthesized compounds were evaluated for their in vitro cytotoxic activity against human tumor breast cancer cell lines. The tested compounds showed moderate to good cytotoxic activity and indeed, some of them were more potent than doxorubicin as a reference drug., (© Georg Thieme Verlag KG Stuttgart · New York.)

Based on the reported anticancer activity of quinolines, a new series of 7-chloroquinoline derivatives bearing the biologically active benzenesulfonamide moiety 2-17 and 19-25 were synthesized starting with 4,7-dichloroquinolne 1. Compound 17 was the most active compound with IC(50) value 64.41, 75.05 and 30.71 µM compared with Doxorubicin as reference drug with IC(50) values 82.53, 88.32 and 73.72 µM on breast cancer cells, skin cancer cells and neuroblastoma, respectively. All the synthesized compounds were evaluated for their in vitro anticancer activity on breast cancer cells, skin cancer cells and neuroblastoma cells. Most of the synthesized compounds showed moderate activity. In order to suggest the mechanism of action for their cytotoxic activity, molecular docking for all synthesized compounds was done on the active site of phosphoinositide kinase (PI3K) and good results were obtained.

To discover new bioactive lead compounds for medicinal purposes, herein, sulfone biscompounds bearing dihydrothiazoles (3-9, 14, 15), acrylamide (11), thiazolidinones (12, 13, 20), thiophenes (16, 17) and benzothiophene (19) were prepared and tested for their anticancer activity. The structures of the products were confirmed from elemental analysis as well as spectral data. All the synthesized compounds showed remarkable anticancer activity against human breast cancer cell line especially, compound (3) with IC50 value 23.02 µM which was better than that of Doxorubicin by three folds. In order to elucidate the mechanism of action of their cytotoxic activity molecular docking on the active sites of farnesyl transferase and arginine methyl transferase was performed for all synthesized compounds and good results were obtained., (© Georg Thieme Verlag KG Stuttgart · New York.)

New quinoline derivatives 6, 7 and 19, pyrimidoquinoline derivatives 8-16 and triazolopyrimidoquinoline derivatives 17 and 18 bearing a bromo-substituent were synthesized starting from 3-(4-Bromophenylamino)-5,5-dimethylcyclohex-2-enone 3. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Compounds 9, 11, 17 and 18 showed IC(50) values (36.4, 39.7, 39.02 and 36.4 μM, respectively) comparable to that of the reference drug doxorubicin (IC(50) = 32.02 μM). On the other hand, compound 6, 14 and 19 exhibited better activity than doxorubicin with IC(50) values of 8.5, 23.5 and 23.7 μM. Additionally, the most potent compounds 6, 14 and 19 were evaluated for their ability to enhance the cell killing effect of γ-radiation.

The present work reports the synthesis of some new Schiff bases, 5-(substituted benzylideneamino)-6-cyano-7H-7-(4-methoxyphenyl)-2-(4-sulphamoylphenylamino) pyrano[2,3-d]thiazole (5-15). The design of the structures of these compounds complies with the general pharmacophoric requirements for CA inhibiting anticancer drugs. The newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Most of the screened compounds showed interesting cytotoxic activities compared to doxorubicin as a reference drug. Compounds 4, 6-8 and 11 (IC(50): 27.51, 10.25, 9.55, 9.39 and 9.70 μM, respectively) exhibited higher cytotoxic activities than the reference drug doxorubicin (IC(50): 32.00 μM). Additionally, the previously mentioned compounds were evaluated again for their ability to enhance the cell killing effect of γ-radiation., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Eighteen new 4-[2-amino-3-cyano-5-oxo-4-substitutedaryl-4H-indeno[1,2-b]pyridin-1-(5H)-yl]benzenesulfonamide derivatives 6a-q were synthesized via a reaction of aromatic aldehydes, enaminone 3 and malononitrile in one-pot reaction. Also, compounds 6a-q were obtained, via another route by reaction of enaminone 3 with arylidenemalononitriles 4a-q. The structure of the synthesized compounds was characterized by microanalysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data. All the target compounds were subjected to in vitro anticancer activity against breast cancer cell line (MCF7). Compound 6d showed a higher potency with IC(50) value (4.34 μM) than that of the doxorubicin (5.40 μM), as the reference drug, while compound 6n with IC(50) value (6.84 μM) is nearly as active as doxorubicin. Also, compounds 6a-c, 6e, 6f, 6h and 6p exhibited a moderate activity, while compounds 3, 6g, 6i-m, 6o and 6q showed weak activity.

2-Cyano-N'-[1-(2,5-dimethoxyphenyl)]ethylideneacetohydrazide 1 was obtained via reaction of cyanoacetic acid hydrazide with 2,5-dimethoxyacetophenone. A number of novel pyridines 2a-j, 3, 4, thiophenes 5-9 and thiazoles 10-12 were prepared by using the hydrazide-hydrazone derivative 1 as a starting material. The structure of the newly synthesized compounds was characterized by elemental analyses, IR, (1)H-NMR, (13)C-NMR and mass spectral data. All the target compounds were subjected to in vitro antitumor activity against Ehrlich ascites carcinoma (EAC) cells. Compounds 2j and 6 showed a higher activity with IC(50) values (54.54, 61.57 μM), 8 when compared with a reference drug IC(50) value (68.99 μM), while compound 5 is nearly as active as doxorubicin (CAS 23214-92-8).