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Aims: The current study aimed to synthesize novel pyrazolo[1,5-a]pyrimidines based on 5- aminopyrazoles 3, evaluate their antimicrobial activity, and study the minimum inhibitory concentration (MIC) for the most active compounds. In addition, molecular docking studies and RNA polymerase inhibitory activity were determined. Background: Starting with our previously reported 5-aminopyrazoles 3, a number of novel pyrazolo[1,5- a]pyrimidines were synthesized. Due to the similarity of pyrazolopyrimidine derivatives with the purine systems, pyrazolopyrimidines are important in many different biological applications, most notably as anti-tumor, antibacterial, and hepatitis C virus inhibitors. The pharmaceutical applications of the pyrazolopyrimidine derivatives were explained in several approved drugs like Indiplon, Zaloplan, and Ocinaplon. Objective: To prepare a novel antimicrobial agent, namely pyrazolo[1,5-a]pyrimidine, reveal their structures using different spectral data, the minimum inhibitory concentration (MIC) for the most active compounds was evaluated, and both the molecular docking and the RNA polymerase inhibitory activity were determined. Methods: A number of different pyrazolopyrimidines namely 2-(phenylamino)-6,11-dihydrobenzo[g]pyrazolo [1,5-a]quinazoline-3-carboxamides (5a-c), (E)-5,7-dimethyl-2-(phenylamino)-6-(phenyldiazenyl)pyrazolo-[1,5- a]pyrimidine-3-carboxamides (7a-c), 7-amino-2-(phenylamino) pyrazolo[1,5-a]pyrimidine-3-carboxamides (11af), 7-amino-2-(phenylamino)-5-(2-thienyl)pyrazolo[1,5-a]pyrimidine-3-carboxamides (14-f) and ethyl 7-amino-3- carbamoyl-2-(phenylamino)-5-(4-pyridyl)pyrazolo[1,5-a]pyrimidine-6-carboxylate derivatives (14g-i) were synthesized through the reaction of 5-aminopyrazoles 3 with a variety of chemical reagents. On the other hand, the evaluation of the antimicrobial activity for all the prepared compounds was screened through different strains as Gram-positive bacteria, such as staphylococcus aureus and Streptococcus mutans, and Gram-negative bacteria, such as Escherichia coli, Pseudomonas aeruginosa, and klebsiella. The antifungal activity was determined by Candids Albicans fungal strain, and the MIC of the most active compounds was measured. The molecular docking was recorded, and the RNA polymerase inhibitory activity was estimated for the high docking score compounds. Results: Compounds 5a, 5b, 5c, 7a, 7b, 7c, 11d, 14b, and 14h were the most active compounds against some of the bacterial and fungal tested strains. MIC was determined for the most active tested compounds. As an antimicrobial agent, compound 7b was the most potent, with a high docking score and RNA polymerase inhibitory activity (IC50= 0.213 μg/ml) compared to Rifampicin (IC50= 0.244 μg/ml). The reactivity of the latter compound was attributed to the presence of 4-Br-C6H4 moiety. The results demonstrated that docking studies on the most active compounds in the RNA polymerase active site were consistent with in vitro assays. Conclusion: The resultant novel bioactive pyrazolo[1,5-a]pyrimidine derivatives were synthesized based on 5- aminopyrazole derivatives 3. The current study evaluated the antimicrobial activity for all the prepared compounds, followed by the determination of the MIC for the most potent active compounds. The molecular docking study was performed, and it was appropriate with the in vitro activity. The RNA polymerase inhibitory activity was assessed for the most active antimicrobial compounds with a high docking score (7b, 7c, 14a, 14b, 14e, 14i). Compound 7b was the most potent compound inhibiting RNA polymerase enzyme compared to the reference drug Rifampicin. Other: The novel prepared heterocyclic systems are extremely important in a variety of domains, especially biological and pharmacological ones.

Background: Due to their biological applications, many tetrahydrobenzo[d]thiazole derivatives were considered the most important class of heterocyclic compounds. There are many drugs known in the market containing the thiazole moiety responsible for the high drug activity. Objective: This work aimed to produce novel heterocyclic compounds such as pyrazole, isoxazole, thiophene, chromeno[7,8-d]thiazole, and thiazolo[4,5-h]quinoline derivatives. The newly synthesized heterocyclic compounds were evaluated against anticancer cell lines followed by c-Met enzymatic activity and tyrosine kinases inhibition for the most active compounds. Methods: In this work, the 3-phenyl-2-thioxo-2,3,5,6-tetrahydrobenzo[d]thiazol-7(4H)-one (3) was synthesized through the reaction of cyclohexane-1,3-dione with phenyl isothiocyanate and elemental sulfur. Compound 3 showed interesting activity toward some chemical reagents producing new heterocyclic compounds that can not be obtained another way. The newly synthesized compounds were evaluated towards the six cancer cell lines. The most active compounds were selected and tested toward the c-Met enzyme by taking foretinib as the positive control. Also, the inhibitions toward the PC-3 cell line using the reference SGI-1776 were measured. Finally, the inhibitions towards the five tyrosine kinases were also tested. Results: The synthesized quinoline and chromene derivatives were evaluated toward the c-Met enzyme using foretinib as the positive control. The obtained results showed that twelve compounds exhibited IC50 values less than 1.30 nM. On the other hand, sixteen compounds showed higher inhibitions than the reference SGI-1776 (IC50 4.86 nM) toward the PC-3 cell line. Conclusion: Novel, heterocyclic compounds were synthesized with a high impact on biological activities. All synthesized compounds were screened for their anti-proliferative effect, and most of them revealed high potent effects. In addition, the c-Met and prostate cancer cell line PC-3 inhibitions for the most active compounds showed that these compounds exhibited high inhibitions. Anti-proliferative activity of selected compounds toward cancer cell lines classified according to the disease showed that most compounds exhibited high inhibitions.

The title compound, C23H15BrN2OS, was the unexpected product in an attempted synthesis of the isomeric 3-(benzo[d]thiazol-2-yl)-6-bromo-1-p-tolylquinolin-2(1H)-one. The Cchromene=N—C angle is wide [125.28 (8)°]. The benzothiazole and chromene ring systems are almost coplanar, with their planes parallel to (1\overline{1}0); the toluene ring system is rotated by ca 40° out of the chromene plane. The molecular packing involves layers with π-stacking, borderline `weak' hydrogen bonds and possible C—H...π contacts.

Aims: Producing novel pyrazolotriazines such as pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[5,1-c][1,2,4]triazine derivatives and evaluate their biological activity as antimicrobial agents followed by the Minimum Inhibitory Concentration (MIC) for the most active compounds. Moreover, study the molecular docking and the RNA polymerase inhibitory activity. Background: Pyrazolotriazine derivatives considered one of the most important heterocyclic compounds due to their broad biological activities. Due to the similarity with the purines and thioguanines, the pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[5,1-c][1,2,4]triazine compounds were used as antimetabolic agents. Moreover, many approved drugs contain pyrazolo[1,5- a][1,3,5]triazine ring systems such as (1882L04 and SB-H02), which confirmed the pharmaceutical applications. The key precursor 5-aminopyrazoles 3 which were firstly synthesized by our research group, were used to prepare the novel pyrazolotriazine derivatives. Objective: This study aimed to synthesize novel bioactive pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[5,1- c][1,2,4]triazine derivatives as antimicrobial agents. Also, the Minimum Inhibitory Concentration (MIC) for the most potent compounds was evaluated. On the other hand, the molecular docking study and the RNA polymerase inhibitory activity were measured. Methods: In this work, the 5-aminopyrazoles 3 were used to synthesize 4-amino-7-(arylamino)pyrazolo[1,5- a][1,3,5]triazine-8-carboxamides 7a-c, 4-amino-7-(arylamino)-2-thioxo-1,2-dihydropyrazolo[1,5-a][1,3,5]-triazine- 8-carboxamides 10a-c and 4-amino-3-cyano-7-(aryllamino)pyrazolo[5,1-c][1,2,4]triazine-8-carboxamides 12ac. The newly resultant compounds were evaluated as antibacterial agents by using (Gram-positive bacteria) such as [Staphylococcus aureus and Streptococcus mutans], and (Gram-negative bacteria) such as [Escherichia coli, Pseudomonas aeruginosa, and Klebsiella]. Moreover, the new compounds were evaluated as antifungal agents by using Candids Albicans fungal strain. Also, the Minimum Inhibitory Concentration (MIC) for the most potent compounds was measured. For all the synthesized compounds, the molecular docking studies were recorded and the RNA polymerase inhibitory activity was measured for the high docking score compounds. Results: The results revealed that most of the prepared compounds such as 7b, 10b, 10c, 12a, 12b, and 12c showed moderate activity towards some of the used strains. The MIC evaluations were recorded for the most active tested compounds 7b, 10b, 10c, 12a and 12c. On the other hand, the most potent and the high docking score compounds (10c, 12a and 12c), were measured in vitro to inhibit RNA polymerase enzyme. Conclusion: A number of novel bioactive pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[5,1-c][1,2,4]triazine derivatives were synthesized. All the resultant compounds were screened for their antimicrobials activity and the MIC test was measured for the most potent compounds. In addition, the in vitro to inhibit RNA polymerase enzyme was evaluated for the most active high docking score compounds. Other: Most of the heterocyclic ring systems have remarkable activities in all fields, especially in pharmaceutical applications.

The dissipation behaviour and the consumer risk assessment of spitotetramat, flonicamid, imidacloprid and pymetrozine in open field strawberries were studied. Insecticides were applied at the authorised levels and the more critical good agricultural practice regimes (GAP). The initial concentrations varied from 0.069 to 1.75 mg kg���1 depending on the compound, while the dissipation half-lives and terminal residues, 14 days from the last applications, were similar. After application according to the authorised pattern the half-lives were 2.8 days for flonicamid and 3.2 days for spitotetramat, imidacloprid and pymetrozine. The dietary risk assessment, performed using the hazard quotient and the EFSA PRIMo model showed no concern to consumer health with exposure values

In this study a new compound 6,6'-(((phenylmethylene,o-olieat)bis(oxy))bis(ethane-2,1-diyl))bis(2-phenyl-o-olieat-1,3,6-dioxazocane)) named (SB2) was synthesized and characterized by FT-IR, TGA, 1H...

Obedience to the aspects of green chemistry and due to its high catalytic potency, ecofriendly synthesis of palladium nanoparticles (PdNPs) was performed using pectin versus acacia gum as polysaccharides. The viscous solution of alkali solubilized polysaccharides acted superiorly in stabilization of MNPs by decreasing their Brownian motions and sequentially decreased their collision and coagulation. Production of PdNPs preliminary was confirmed via UV–visible spectra. Zetasizer and transmission electron microscopy data, the particle size of PdNPs were prepared by pectin (27.9 nm) is larger than that by acacia gum (5.3 nm). XRD and FT-IR data affirmed the redox reaction between biopolymers and metal ions to produce PdNPs. PdNPs synthesized by acacia gum were characterized by higher surface area (19.54 m2/g) compared to that prepared by pectin (3.67 m2/g). Additionally, PdNPs synthesized by acacia gum were exhibited by fastest rate of dye discoloration, resulting in complete reductive discoloration of dye after only 5 min and t1/2 was estimated to be 1.70 min, while, k1 was 408.8 × 10−3 min−1. The presented green technique could be successively applicable for synthesis of size regulated catalytically active PdNPs to be employable in various industrial purposes.

In the title compound, C16H9NO2S, the interplanar angle is 6.47 (6)°. An intramolecular S...O=C contact of 2.727 (2) Å is observed. The packing is determined by several types of weak interaction (`weak' hydrogen bonds, S...S contacts and π–π stacking).

In the title compound, C

PurposeThis work aims to synthesize a series of novel acyclic and/or heterocyclic systems, as precursors for dyes with potential antimicrobial activity that could be used for simultaneous dyeing and antimicrobial textile finishing. Thus, a series of novel pyridine, thiophene and pyrazolo[3,4-b]pyridine derivatives were synthesized, and their antimicrobial and textile finishing properties were studied and evaluated.Design/methodology/approachThe synthesis, structure elucidation and antimicrobial activities of the newly synthesized compounds based on 4,4-dicyano-3-phenyl-but-3-enoic acid phenylamide (1) were demonstrated. The minimal inhibitory concentration in μg/mL of the compounds showed significant antimicrobial activity against most of the tested organisms. On the other hand, their spectral characteristics and fastness properties were measured and evaluated. Antimicrobial activities of the dyed fabrics in terms of inhibition zones (mm) were measured and evaluated.FindingsA series of novel heterocyclic compounds (Schemes 1-3) were synthesized based on starting material (1). Compounds (1), 2, 4a, 8a and 9c exhibited comparable or even higher antibacterial activities than the selected standards (ampicillin), while compounds 2, 3c, 3d, 4a and 8b revealed higher antifungal activities than the selected standard (cycloheximide). On the other hand, some dyes showed high antimicrobial evaluation on the dyed fabrics (nylon 66, acetate and polyester) expressed as size (mm) of inhibition zones (Tables I-IV).Practical implicationsResults revealed that many hydrazo and azo derivatives were synthesized from some pyridines and thiophenes. The antimicrobial evaluation and textile finishing of the newly synthesized products revealed significant and potent values of antimicrobial activity.Originality/valueAll the synthesized compounds were novel and most of them exhibited higher antimicrobial activities than the selected standards antibiotics, thus are valuable for simultaneous dyeing and antimicrobial functional finishing of textile fabrics.

This study aimed to synthesize new polymeric additives including homo- and co-polymers based on 4-methyl-2-oxo-2H-chromen-7-yl methacrylate monomer and evaluating their activity as potential antimicrobials and as pour-point depressants for modification of waxy crude oil rheology. The resultant compounds were characterized by their IR, 1H NMR and 13C NMR spectral data. The formation of the new polymers, namely, poly(7-methacryloyloxy-4-methylcoumarin) [poly(MAOMC)] homo-polymer, poly(7-methacryloyloxy-4-methylcoumarin-co-vinylacetate) [poly(MAOMC)-co-(VA)] and poly(7-methacryloyloxy-4-methylcoumarin-co- octadecyl 4-(methacryloyloxy)benzoate) [poly(MAOMC)-co-(OMAOB)] co-polymers was based on free radical polymerization. The polymerization reaction was carried at 70±2°C using 2,2’-azobisisobutyronitrile (AIBN) as an initiator and dimethylformamide (DMF)/toluene as a solvent in the case of homo-polymer [poly(MAOMC)] and co-polymer [poly(MAOMC)-co-(VA)], while polymerization proceeds at the same temperature by using benzoyl peroxide as an initiator and toluene as a solvent in the case of co-polymer [poly(MAOMC)-co-(OMAOB)] The activities of the resultant compounds as potential antibacterial agents were evaluated against the two Gram-positive (Bacillus cereus and Staphylococcus aureus), the four Gram-negative (Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Salmonella typhimrium) bacterial strains, and as antifungal agents against two fungal species (Aspergillus flavus and Candids albicans). The results showed that MAOMC monomer and poly(MAOMC)-co-(OMAOB) copolymer indicated moderate potent activity towards the bacterial and fungal strains used. At the other extreme, the influence of coumarin and octadecyl benzoate based compounds on the pour-point depression and on the rheological properties of crude oil with low asphaltene content was studied. The results indicated that all three polymers exhibited very good efficiency as additives to improve the flow-ability of the tested crude oil. Moreover, the poly(MAOMC)-co-(OMAOB) co-polymer was found to exhibit the highest performance to reduce and depress the pour-point of the tested crude oil and decrease the viscosity to a large extent due to the presence of two aromatic units with the long aliphatic carbon chain in its structure.

Many studies mentioned that Melatonin considers an anti-cancer agent. So in this study, a lot of novel Melatonin derivatives incorporated different heterocyclic ring systems such as triazole, thiadiazole, tetrazole, thiazole, thiophene and pyrazole were synthesized. The synthesized compounds 5, 6, 8, 11, 15, 16 and 19 were evaluated as anti-cancer by using two human cancer cell lines, Breast cancer (MCF7) and colon cancer (HCT-116). The synthesized compounds showed a gradual decrease in the cell viability of the two cell lines. We also observed that compound 16 was the lowest IC50 and the highest cytotoxic effects against the two cancer cell lines. Furthermore, the molecular-docking study was employed to determine the possible mode of action of the synthesized compounds against proteins (CDK2 and P53-MDM2) which, were considered to be potential proteins involved in the pathogenesis of cancer. We observed that compound 16 was the best-docked ligand against the targeted proteins, as it displayed the lowest binding energies, critical hydrogen bonds, and hydrophobic interactions compared to other tested compounds.

Amira EM Abdallah, Galal H Elgemeie Department of Chemistry, Faculty of Science, Helwan University, Helwan, Cairo, Egypt Background: Over the years, pyrazolopyrimidine derivatives have been recognized as having antimicrobial activities. Recently, we reported different synthetic methods to prepare pyrazolopyrimidine derivatives as anticancer and antimicrobial agents. The studies showed that our previously reported 5-aminopyrazoles 2 act as a building block for the preparation of a variety of interesting pyrazolopyrimidines as purine analogs. Purpose: The objective of this study was to describe the direct new method for preparation of novel pyrazolo[1,5-a]pyrimidine derivatives and their corresponding cycloalkane ring-fused derivatives. Also, the new compounds were tested in vitro for their antibacterial and antifungal activity properties. Methods: Pyrazolo[1,5-a]pyrimidine derivatives were prepared by the reaction of our previously reported 5-aminopyrazoles 2 with suitable sodium salts of (hydroxymethylene) cycloalkanones and sodium salts of unsaturated ketones. Results: The structures of the new compounds were characterized according to their mass spectroscopy, 1H NMR, IR and elemental analyses. Compounds 8b, 10e, 10i, and 10n were the most active compounds against Gram-positive and Gram-negative bacterial species. Compound 10i with two moieties of 4-Br-C6H4 revealed increased reactivity compared with ampicillin as standard reference. Conclusion: About twenty two novel pyrazolo[1,5-a]pyrimidine derivatives and their corresponding cycloalkane ring-fused derivatives were prepared through the reaction of 5-aminopyrazoles 2 with different sodium salts of (hydroxymethylene) cycloalkanones and sodium salts of unsaturated ketones. The antibacterial and antifungal activities of the newly synthesized compounds were evaluated and revealed that compounds 8b, 10e, 10i, and 10n were the most active compounds against Gram-positive and Gram-negative bacterial strains. Keywords: pyrazolo[1,5-a]pyrimidines, 5-aminopyrazoles, 2-(hydroxymethylene)-1-cycloalkanones, 2-formylcycloalkanones, antibacterial, antifungal, docking studies

The reactivity of compounds 2-(1-(2-chloroacetyl)-1H-benzo[d]imidazol-2-yl)acetonitrile 2 and 3-(1-(2-chloroacetyl)-1H-benzo[d]imidazol-2-yl)-2H-chromen-2-one 8 towards different chemical reagents were studied and a series of novel benzimidazole derivatives were obtained (2-6a-d and 8-12a-d). Moreover, in vitro growth inhibitory effect of the newly synthesized compounds were evaluated in term of [IC50 µM] against the six cancer cell lines, human lung carcinoma (A549), lung cancer (H460), human colorectal (HT29), gasteric cancer cell (MKN-45), glioma cell line (U87MG) and cellosaurus cell line (SMMC-7721) where foretinib was used as standard reference. The results showed that compounds 2 (only for A549 cell line), 3a, 4, 6c, 6d, 8, 9a, 9e and 9f were the most active compounds towards the six cancer cell lines. On the other hand, the toxicity of these most potent compounds against shrimp larvae indicated that compounds 3a, 4, 6d, 9e and 9f were non toxic while compounds 6c and 8 were very toxic and compounds 2 and 9a were harmful against the tested organisms.

Reactivity of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carbonitrile towards thioglycolic acid resulted in thiazole derivative 1. The latter reacted with different chemical reagents to give thiazole, pyrano[2,3-d]thiazole and thiazolo[ 4,5-d]thiazole derivatives. Cytotoxicity effects of the newly synthesized products against six cancer cell lines, namely, human gastric cancer (NUGC), human colon cancer (DLD- 1), human liver cancer (HA22T and HEPG-2), human breast cancer (MCF) and nasopharyngeal carcinoma (HONE-1) as well as against a normal fibroblast cell (WI-38) were evaluated. The study showed that the 4,5,6,7 tetrahydrobenzo[ b] thiophene derivatives 6a, 7, 8a,b, 9b and 10b,c w ere t he most active compounds. Their potencies were attributed to the presence of the electron withdrawing groups.

The 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene was the key starting compound used to synthesize new thiazole, pyrimidine, pyran, pyridine and thiazine derivatives. The cytotoxicity of the synthesized compounds was studied towards the three cancer cell lines namely MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (central nervous system (CNS) cancer) in addition to the normal cell line (WI-38) using doxorubicin as the reference drug. The study showed that compounds 5, 9a, 15b, 17c, 18 and 21b were the most potent compounds.

Hetero-steroids, hybrid anticancer agents, have received much interest in view of their numerous and promising biological activities. In this study, a novel class of hetero-steroids were synthesized, analytical and spectral data proved the validity of the novel synthesized steroid derivatives. The cytotoxicity of the synthesized compounds 2, 5, 6, 7, 10, 11, 12, 14, 15, 17 were evaluated using human hepatocellular carcinoma cell lines (HepG2 and Huh-7) and non-small cell lung cancer (A549) cell lines. The synthesized compounds reported a remarkable gradual decrease in the cell viability of the three tested cancer cell lines. It was observed that compounds 2 and 12 had the lowest IC50s and the highest cytotoxic effects against all tested cell lines. As attempt to explain the cytotoxic activity achieved by the tested compounds in the in vitro study, molecular simulation was done to reveal the activity of the tested compounds against four different proteins (CDK2, CYP19, JAK2, and BCL2) which are highly implicated in cancer regulation and progression. We found that compound 2, and 12 were the best docked compounds against all tested receptors, which was indicated by lowest binding energy compared to reference ligand. Interestingly enough, our molecular study was in agreement with the cytotoxic activity. As future prospective, we are recommending further study on compounds 2, and 12 against the four different proteins to prove their mode of action.

This work was focused on an investigating of flow ability of waxy crude oil by nontraditional polymer compound. For this propose, a spirocompound consisted of benzaldehyede and triethanolamine 6,6'-(((phenylmethylene) bis (oxy)) bis (ethane-2,1-diyl)) bis (2-phenyl-1,3,6-dioxazocane) [SB] was synthesized using zeolite as a catalyst. The chemical structure of the [SB] was investigated by FT-IR, TGA,GPC, H1NMR and Mass spectroscopy. The rheological behavior and pour point depression of waxy crude oil were also studied different dosages and temperatures. The results showed a significant reduction in the viscosity at different temperatures and dosages. Moreover, it was noticed a decrease in the apparent viscosity and the Bingham yield value for [SB] 437.7, 367.1, and 307.1 cp and 0.48, 0.39 and 0.31 Pa at 15 oC, 20 oC and 30 oC and concentration 1000 ppm respectively. While the blank experiment displayed 743.1, 694.2 and 607.2 cp and 0.74, 0.69 and 0.60 Pa at the same temperatures. This study included blends between [SB] and the acrylate based polymers abbreviated as (B1, B2, B3 and B4). Furthermore, the rheological behavior and the pour point for these blends exhibited that the blend [B4] shew more reduction in the apparent viscosity than [SB] being alone. The apparent viscosity and yield value for [B4] were; 267.8, 249.2 and 212.7 cp and 0.22, 0.11 and 0.09 Pa at 15oC, 20oC and 30oC and concentration 1000 ppm respectively. The pour point depression (Δpp) of [SB] was 9oC while the blank pour point was 27 o C and the B4 was achieved the maximum depression in the pour point (Δpp= 18 o C) at a concentration of 1000 ppm. This result means that the addition of [SB] to [B4] showed the most positive synergistic effect.

The reaction of ethyl cyanoacetate 2 with o -phenylenediamine 1 gave the 2-cyanomethylbenzo[ c ]imidazole 3. The latter compound was used as the key starting material to synthesis biologically active heterocyclic derivatives. Thus, the reaction of compound 3 with cyclohexanone 4 and either of benzaldehyde ( 5a ), 4-methoxybenzaldehyde ( 5b ) or 4-chlorobenzaldehyde ( 5c ) gave the annulated derivatives 6a-c , respectively. The antitumor evaluations of the newly synthesized products against the three cancer cell lines MCF-7 (breastadeno-carcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer) showed that compounds 6b , 12 , 22b , 22c , 25 , 32 , 33 and 35 exhibited optimal cytotoxic effect against cancer cell lines, with IC 50 ’s in the nM range. Bioactive compounds are often toxic to shrimp larvae. Thus, in order to monitor these chemicals’ in vivo lethality to shrimp larvae ( Artemiasalina ), Brine-Shrimp Lethality Assay was used. Compounds 22b, 25 and 33 showed non toxicity against the tested organisms.

Attempting to produce cyclized systems with potential anti-proliferative activity, a series of novel thiophene and benzothiophene derivatives were designed and synthesized. The reactivity of the latter derivatives towards different chemical reagents was studied. Twenty-one compounds were synthesized and evaluated as anti-cancer agents. The results showed that ethyl 5-amino-3-(4-chlorostyryl)-4-cyanothiophene-2-carboxylate (5b), ethyl 5-amino-4-((4-methoxyphenyl)carbonyl)-3-methylhiophene-2-carboxylate (8c) and 5-3-(ethoxy-3-oxopropanamido)-3-methyl-4-(phenylcarbamoyl)thiophene-2-carboxylate (9) were the most active compounds towards three tumor cell lines – MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer) and a normal fibro-blast human cell line (WI-38) compared to the anti-proliferative effects of the reference control doxorubicin.

Background Over the years, pyrazolopyrimidine derivatives have been recognized as having antimicrobial activities. Recently, we reported different synthetic methods to prepare pyrazolopyrimidine derivatives as anticancer and antimicrobial agents. The studies showed that our previously reported 5-aminopyrazoles 2 act as a building block for the preparation of a variety of interesting pyrazolopyrimidines as purine analogs. Purpose The objective of this study was to describe the direct new method for preparation of novel pyrazolo[1,5-a]pyrimidine derivatives and their corresponding cycloalkane ring-fused derivatives. Also, the new compounds were tested in vitro for their antibacterial and antifungal activity properties. Methods Pyrazolo[1,5-a]pyrimidine derivatives were prepared by the reaction of our previously reported 5-aminopyrazoles 2 with suitable sodium salts of (hydroxymethylene) cycloalkanones and sodium salts of unsaturated ketones. Results The structures of the new compounds were characterized according to their mass spectroscopy, 1H NMR, IR and elemental analyses. Compounds 8b, 10e, 10i, and 10n were the most active compounds against Gram-positive and Gram-negative bacterial species. Compound 10i with two moieties of 4-Br-C6H4 revealed increased reactivity compared with ampicillin as standard reference. Conclusion About twenty two novel pyrazolo[1,5-a]pyrimidine derivatives and their corresponding cycloalkane ring-fused derivatives were prepared through the reaction of 5-aminopyrazoles 2 with different sodium salts of (hydroxymethylene) cycloalkanones and sodium salts of unsaturated ketones. The antibacterial and antifungal activities of the newly synthesized compounds were evaluated and revealed that compounds 8b, 10e, 10i, and 10n were the most active compounds against Gram-positive and Gram-negative bacterial strains.