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Background: Chalcones, originated from natural product, have been broadly studied their biological activity against various proteins which at the molecular level, are responsible for the progress of the diseases in cancer (e.g. kinases), inflammation (oxidoreductases), atherosclerosis (cathepsins receptor), and diabetes (e.g. α-glucosidase)., Objective: Here we synthesize 10 chalcone derivatives to be evaluated their in vitro enzymatic inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)., Methods: The synthesis was carried out using Claissen-Schimdt condensation and the in vitro assay was conducted using Ellman Method., Results: Compounds 2b and 4b demonstrated as the best IC 50 of 9.3 μM and 68.7 μM respectively, towards AChE and BChE inhibition. Molecular docking studies predicted that this activity might be due to the interaction of the chalcones with important amino acid residues in the binding site of AChE such as SER200 and in that of BChE, such as TRP82, SER198, TRP430, TYR440, LEU286 and VAL288., Conclusion: Chalcone can be used as the scaffold for cholinesterase inhibitor, in particularly either fluorine or nitro group to be augmented at the para-position of Ring B, whereas the hydrophobic chain is necessary at the meta-position of Ring B., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The inhibition of α-amylase enzyme is one of the best therapeutic approach for the management of type II diabetes mellitus. Chalcone possesses a wide range of biological activities., Objective: In the current study chalcone derivatives (1-16) were synthesized and evaluated their inhibitory potential against α-amylase enzyme., Methods: For that purpose, a library of substituted (E)-1-(naphthalene-2-yl)-3-phenylprop-2-en-1-ones was synthesized by Claisen-Schmidt condensation reaction of 2-acetonaphthanone and substituted aryl benzaldehyde in the presence of base and characterized via different spectroscopic techniques such as EI-MS, HRESI-MS, 1 H-, and 13 C-NMR., Results: Sixteen synthetic chalcones were evaluated for in vitro porcine pancreatic α-amylase inhibition. All the chalcones demonstrated good inhibitory activities in the range of IC 50 = 1.25 ± 1.05 to 2.40 ± 0.09 μM as compared to the standard commercial drug acarbose (IC 50 = 1.34 ± 0.3 μM)., Conclusion: Chalcone derivatives (1-16) were synthesized, characterized, and evaluated for their α- amylase inhibition. SAR revealed that electron donating groups in the phenyl ring have more influence on enzyme inhibition. However, to insight the participation of different substituents in the chalcones on the binding interactions with the α-amylase enzyme, in silico (computer simulation) molecular modeling analyses were carried out., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Novel 4-[3-(6/7/8-Substituted 4-Oxo-4H-chromen-3-yl)acryloyl]phenylboronic acid derivatives (5a-h) as well as other 6/7/8-substituted-3-(3-oxo-3-(4-substitutedphenyl) prop-1-enyl)-4H-chromen-4-one derivatives (3a-u) have been designed as p53-MDM2 pathway inhibitors and reported to possess significant cytotoxic properties against several cancer cell lines., Objectives: The current project aims to frame the structure-anticancer activity relationship of chromen-4-on-3-yl chalcones (3a-u/5a-h). In addition, docking studies were performed on these chromeno-chalcones in order to have an insight into their interaction possibilities with MDM2 protein., Methods: Twenty-nine chromen-4-on-3-yl chalcone derivatives (3a-u/5a-h) were prepared by utilizing silica supported-HClO4 (green route with magnificent yield) and tested against four cancer cell lines (HCT116, MCF-7, THP-1, NCIH322)., Results: Among the series 3a-u, compound 3b exhibited the highest anticancer activity (with IC50 values ranging from 8.6 to 28.4 µM) overall against tested cancer cell lines. Interestingly, para- Boronic acid derivative (5b) showed selective inhibition against colon cancer cell line, HCT-116 with an IC50 value of 2.35 µM. Besides the emblematic hydrophobic interactions of MDM2 inhibitors, derivative 5b was found to exhibit extra hydrogen bonding with GLN59 and GLN72 residues of MDM2 in molecular dynamics (MD) simulation. All the compounds were virtually nontoxic against normal fibroblast cells., Conclusion: Novel compounds were obtained with good anticancer activity especially 6- Chlorochromen-4-one substituted boronic acid derivative 5b. The molecular docking study proposed good activity as a MDM-2 inhibitor suggesting hydrophobic as well as hydrogen bonding interactions with MDM2., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Chalcones substituted by methoxyl groups have presented a broad spectrum of bioactivities, including antifungal, antibacterial and antiproliferative effects. However, a clear and unambiguous investigation about the relevance of this substituent on the chalcone framework has not been described., Objective: The purpose of this work is to assess the antibacterial, antifungal and antiproliferative activities of the two series of seventeen synthesized regioisomeric methoxychalcones. Series I and II were constituted by chalcones substituted by methoxyl groups on rings A (5-12) and B (13-21), respectively. In addition, the library of methoxychalcones was submitted to in silico drug-likeness and pharmacokinetics properties predictions., Methods: Methoxychalcones were synthesized and their structures were confirmed by NMR spectral data analyses. Evaluations of antimicrobial activity were performed against five species of Candida, two Gram-negative and five Gram-positive species. For antiproliferative activity, methoxychalcones were evaluated against four human tumorigenic cell lines, as well as human non-tumorigenic keratinocytes. Drug-likeness and pharmacokinetics properties were predicted using Molinspiration and PreADMET toolkits., Results: In general, chalcones of series I are the most potent antifungal, antibacterial and antiproliferative agents. 3', 4', 5'-Trimethoxychalcone (12) demonstrated potent antifungal activity against Candida krusei (MIC = 3.9 μg/mL), eight times more potent than fluconazole (reference antifungal drug). 3'-Methoxychalcone (6) displayed anti-Pseudomonas activity (MIC = 7.8 μg/mL). 2',5'-Dimethoxychalcone (9) displayed potent antiproliferative effect against C-33A (cervix), A-431 (skin) and MCF-7 (breast), with IC50 values ranging from 7.7 to 9.2 μM. Its potency was superior to curcumin (reference antiproliferative compound), which exhibited IC50 values ranging from 10.4 to 19.0 μM., Conclusion: Our studies corroborated the relevance of methoxychalcones as antifungal, antibacterial and antiproliferative agents. In addition, we elucidated influence of the position and number of methoxyl groups toward bioactivity. In silico predictions indicated good drug-likeness and pharmacokinetics properties to the library of methoxychalcones., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Microbial infections is a global public health problem. The aim of this work was to synthesize and evaluate the antimicrobial activity of novel triazoles, morpholines and thiosemicarbazones., Methods: Compounds were synthesized using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. The antimicrobial activity of these compounds against bacteria and yeast was evaluated by the broth microdilution method., Results: The proposed route for synthesis gave high to moderate yields, moreover these compounds were successfully characterized by 1H NMR, 13C NMR and LC-MS. Antimicrobial testing indicated that the thiosemicarbazone and morphine derivatives had the best antimicrobial activity against the microorganisms tested with minimum inhibitory concentrations (MIC) between 0.29 and 5.30 µM. Thiosemicarbazone derivative (12) was able to inhibit the growth of C. tropicalis, with minimum fungicidal concentration (MFC) of 0.55 µM. In addition, this compound was active against E. coli, S. aureus and S. epidermidis, with MIC values ranging from 0.29 to 1.11 µM. Moreover, the morpholine derivative (15) had an MIC value of 0.83 µM against C. albicans and E. coli., Conclusion: We have efficiently synthesized a series of eleven novel triazoles, thiosemicarbazones and morpholine derivatives using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. Thiosemicarbazone derivative (12) showed promising antifungal and antibacterial activity and these findings suggest that this compound can be used as scaffolds to design new antimicrobial drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Chalcones, natural products produced by plants as a natural defense mechanisms against various pathogens, are molecules with structures that include two aromatic rings joined by an α, β unsaturated carbonyl system. Previous research has demonstrated that chalcones exhibit a wide variety of biological activities, including anticancer, antifungal, and antibiotic properties., Objective: Our goal is to synthesize novel heterocyclic-containing chalcones and have their biological activities evaluated. Methods Sixteen chalcones were synthesized by the crossed aldol condensation of substituted tetralones with substituted pyridinylaldehydes. The products were purified by recrystallization in MeOH/H2O and characterized by 1H NMR, 13C NMR, and HRMS. Anticancer assays were performed by NCI (National Cancer Institute) against the NCI-60 panel of 60 different human cancer cell lines, including leukemia, non-small-cell lung cancer, colon, central nervous system, melanoma, ovarian, renal, prostate, and breast cancer. Antimicrobial assays were performed by COADD (Community for Open Antimicrobial Drug Discovery) against Escherichia coli, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, Cryptococcus neoformans var. grubii, and Candida albicans., Result: Chalcone 3d had demonstrated growth inhibition greater than 60% against a variety of cancers: leukemia (MOLT-4, SR), non-small cell lung cancer (NCI-H522), colon cancer (HCT- 116), prostate cancer (DU-145), and breast cancer (MCF7, MDA-MB-468) and was also cytotoxic to three different cell lines (CCRF-CEM, RPMI-8226, and KM12). 5c was active against leukemia (CCRF-CEM, RPMI-8226, SR) and breast cancer (MCF7) and 5e was active only against leukemia (RPMI-8226, SR). 5h was partially active and the best compound with growth inhibition of MRSA by 75%. 3b was the best compound against EC, KP, and PA and 3f had the greatest activity against AB. For fungi, 3f and 3e demonstrated the best growth inhibition., Conclusion: A small library of heterocyclic-containing chalcones was developed and initial screening demonstrates modest activity against cancers, bacteria, and fungi., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Chalcones, 2-pyrazolines and thiazoles have been reported to possess various pharmacological activities., Objective: Synthesis of new chalcones and utilizing them as a building block for constructing a series of thiazole derivatives and evaluating some of them as anticancer agents., Method: The new compounds were synthesized via stirring at room temperature or thermal heating. Cytotoxic evaluation of the new synthesized compounds was tested using the method of Skehan et al. Moreover, the computational studies were performed using MOE 2014.09 software., Result: A series of new chalcones were prepared by the reaction of ethyl 3-acetyl-1-aryl-5-methyl- 1H-pyrazole-4-carboxylate with a number of substituted benzaldehydes. One of these chalcones was used as a building block for constructing a pyrazoline ring via its reaction with thiosemicarbazide. The produced carbothioamide derivative was used for the preparation of two series of thiazole derivatives by its reaction with a number of hydrazonoyl chlorides. Moreover, reaction of 3- acetylpyrazole thiosemicarbazone derivative with a number of N-aryl-2-oxopropane hydrazonoyl chlorides afforded 5-arylazothiazole derivatives. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data. Some of the newly synthesized chalcones and thiazoles were tested for their cytotoxicity against human colon carcinoma cell line (HCT-116) and the molecular docking was carried out on the most active compound 3f., Conclusion: The results of the anticancer activity revealed that compounds 3f, 3e, 3c and 3b have promising activities compared with the standard drug Doxorubicin. Moreover, the computational studies confirm the results of biological activity. Also, the ADME profile study showed that compound 3f can be considered as a promising drug by conducting good pharmacokinetic and medicinal chemistry tests., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Acetylcholinesterase (AChE) is an important target in the development of drug to treat Alzheimer's disease (AD). In this work, we investigated the effect of twenty-two synthesized chalcones on AChE activity., Objective: This work is aimed to synthesize and evaluate the effect of chalcones on the AChE activity, as well as anti-oxidant activity and predict their pharmacokinetic profile., Method: Chalcones were synthesized through a Claisen-Schmidt condensation and their inhibitory effect on the AChE was evaluated by the Elmann's colorimetric method. To determine the anti-oxidant activity the DPPH radical scavenging method was chosen., Results: We found that all chalcones inhibit this activity, with IC50 values ranging from 0.008 to 4.8 µM. We selected the most active compound 19 with an IC50 value of 0.008 µM for a kinetic study demonstrating a competitive inhibition mode. Molecular docking simulations showed a good interaction between 19 and the active site of AChE. Considering the prediction of pharmacokinetic parameters being a useful tool for selecting potential drug candidates, our study results suggest that the majority of chalcones, including the most active one, have a promising pharmacokinetic profile and blood-brain barrier permeability. The involvement of reactive oxygen species (ROS) in AD-related events has encouraged us to evaluate these chalcones as radical scavengers., Conclusion: We have found that compound 19 is a potent AChE inhibitor, and based on kinetic studies, it acts as a competitive inhibitor., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

37 acetylenic chalcones were designed, synthesized by the Pd/Cu catalyzed Sonogashira coupling reaction, and evaluated for anti-inflammatory activities. A majority of these compounds showed remarkable inhibitions of the expression of inflammatory cytokines in LPS-stimulated macrophages. Six of them demonstrated the dose-dependent inhibition of inflammatory cytokines, and 4f is the most potent antiinflammatory compound. Our results suggest that these active acetylenic chalcones could be further developed as promising candidates for the treatment of inflammatory diseases.

A series of piperidyl-thienyl & 2-pyrazoline derivatives of quinolyl-thienyl chalcones were tested to observe the structural characteristics for the monoamine oxidase inhibitory (MAO) activity. In both these series, a diverse range of substituted thiophenes are used which enable the structure activity relationship. The compounds showed enhanced inhibition against MAO-A & B as compared to reference compounds. Compound 1c exhibited most potent MAO-A inhibition having IC50 value of 0.062 µM, while 1j showed excellent inhibitory potency against MAO-B having IC50 value of 0.088 µM. The present investigation demonstrated that among piperidyl-thienyl chalcones, almost all the compounds exhibit significant MAO-A inhibition, thus may have antidepressant activity. Whereas among the 2-pyrazoline derivatives of chal-cones, many compounds revealed MAOB inhibition and hence may be applied in the control of senile dementia. Molecular docking studies were carried out against human MAO-A and MAO-B to rationalize important binding site interactions.

A series of aromatic diketone derivatives were designed and synthesized as potential HIV-1 integrase (IN) inhibitors and evaluated to determine their ability to inhibit the strand transfer process of HIV-1 integrase. The results indicate that (Z)-1-(3-acetyl-2-hydroxy-4,6-dimethoxyphenyl)-3-hydroxy-3-(substituted)phenylprop-2-en-1-one (5a-5d) can moderately inhibit HIV-1 integrase. The cyclization and condensation products (6a-6c and 7e-7f) of compounds 5a-5d show poor inhibitory activity against HIV-1 integrase. The molecular docking results indicate that the different types of compounds act on HIV-1 integrase in different ways, and these results can explain the differences in the inhibitory activities.

Mitochondrial enzymes monoamine oxidases were thought to be an emerging and useful therapeutic target for neurodegenerative disorders. Monoamine oxidases have two isoforms, A and B. MAO-A is related with metabolism of amine neurotransmitters in the brain whereas MAO-B is concerned with aging related neurodegenerative disorders. Therefore the identification, characterization and discovery of potent MAO-A and B inhibitors is very crucial in research. A series of quinolyl-thienyl chalcones were tested against MAO-A and B. Among the screened compounds, most of them revealed potent MAO-A and B inhibition. Compound 5i presented most potent MAO-A inhibition having IC50 values 0.047 µM, while 4l showed excellent inhibitory potency against MAO-B among all the tested compound having IC50 values 0.063 µM. Molecular modelling studies were performed against human MAO-A and MAO-B for the explanation of binding site interactions.

Chalcones are a group of plant-derived polyphenolic compounds possessing a wide variety of biological activities. The aim of this study was to synthesize 2,6-dihydroxy-4-isopentenyloxychalcone (1), a chalcone found in plants belonging to the genera Helichrysum, Pleiotaxix and Metalasia, and evaluate its antimicrobial effects against major oral pathogens as well as its anti-inflammatory properties. Compound 1 was synthesized using a simple two-step procedure. Among the seven pathogens tested, Porphyromonas gingivalis and Prevotella intermedia were the most susceptible to inhibition by 1. This chalcone also attenuated the secretion of interleukin-8 and chemokine (C-C motif) ligand 5 (CCL5) by lipopolysaccharide (LPS)-stimulated oral epithelial cells as well as the secretion of matrix metalloproteinase 2 (MMP-2) by LPS-stimulated gingival fibroblasts. In conclusion, our study showed that 1 exerts a dual effect by acting on both oral pathogens and the host inflammatory response and thus represents a molecule of interest for periodontal infections.

A series of 2´-hydroxy-4´-isoprenyloxychalcone derivatives was synthesized and evaluated for its antidepressant- like activity using the FST and TST. All compounds exhibited the potential antidepressant-like activity in the FST and the TST through intraperitoneal injection. Among them, compounds 4i, 4l and 4n exhibited more potent antidepressant- like activity at a dose of 10 mg/kg. And, compounds 4i, 4l and 4n were also adequately absorbed in mice after oral administration at a dose of 30 mg/kg. In the 5-HT induced head-twitch test and yohimbine induced mortality test, compound 4i could increase the head-twitch and rise mortality in mice. The results suggested that the antidepressant effects of compound 4i may be related to via the serotonergic and noradrenergic system.

It has been shown that some chalcones are able to inhibit tubulin polymerization, giving cytotoxicity and destruction of tumoral vasculature. A library of 180 novel chalcone analogs has been synthesized via click chemistry and screened for their cytotoxicity and tubulin assembly inhibition. 10 out 180 click chalcones displayed low micromolar cytotoxicity but only compound Nf depicted antitubulin activity. While Nf displayed only micromolar potency this result shows click-chalcones may be anti-tubulin agents and validate this strategy to search for novel active chemical entities.

Chalcones and Mannich bases have been reported to present antiinflammatory activities as well as inhibitory activities on several factors implicated in inflammation disorders. A series of chalcones and some related Mannich bases were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde. Mannich bases were derived from chalcones, with formaldehyde and the corresponding amine. The compounds were tested in vitro for their ability to inhibit various enzymes involved in the arachidonic acid cascade, for their antioxidant behaviour and in vivo for anti-inflammatory activity. Some chalcones and Mannich bases present strong anti-inflammatory and antioxidant activities. Almost all the tested compounds present high inhibitory activity on lipid peroxidation. Some compounds showed potent inhibitory effect on superoxide anion formation. Among the tested compounds 5 and 6 showed the highest lipoxygenase (LO) inhibitory activity. All the tested compounds inhibit both the proteolytic and esteratic activities of trypsin and chymotrypsin. The results indicated that the anti-inflammatory effects of the compounds were partially mediated, through their antioxidant activity. Attempts to correlate quantitatively structure with activity revealed that lipophilicity and molar refractivity influence the biological response.

The antileishmanial and antimalarial activity of methoxy-substituted chalcones (1,3-diphenyl-2-propen-1-ones) is well established. The few analogs prepared to date where the 3-phenyl group is replaced by either a pyridine or naphthalene suggest these modifications are potency enhancing. To explore this hypothesis, sixteen 3-naphthalenyl-1-phenyl-2-prop-1-enones and ten 1-phenyl-3-pyridinyl-2-prop-1-enones were synthesized and their in vitro efficacies against Leishmania donovani and Plasmodium falciparum determined. One inhibitor with submicromolar efficacy against L. donovani was identified (IC50 = 0.95 microM), along with three other potent compounds (IC50 < 5 microM), all of which were 3-pyridin-2-yl derivatives. No inhibitors with submicromolar efficacy against P. falciparum were identified, though several potent compounds were found (IC50 < 5 microM). The cytotoxicity of the five most active L. donovani inhibitors was assessed. At best the IC50 against a primary kidney cell line was around two-fold higher than against L. donovani. Being more active than pentamidine, the 1-phenyl-3-pyridin-2-yl-2-propen-1-ones have potential for further development against leishmaniasis; however it will be essential in such a program to address not only efficacy but also their potential for toxicity.