Design, synthesis, and antitumor screening of new thiazole, thiazolopyrimidine, and thiazolotriazine derivatives as potent inhibitors of VEGFR-2.

New thiazole, thiazolopyrimidine, and thiazolotriazine derivatives 3-12 and 14a-f were synthesized. The newly synthesized analogs were tested for in vitro antitumor activity against HepG2, HCT-116, MCF-7, HeP-2, and Hela cancer cells. Results indicated that compound 5 displayed the highest potency toward the tested cancer cells.

Design, synthesis, and evaluation of new benzimidazole‏ ‏‎thiourea ‎derivatives as antitumor agents.

Novel benzimidazole thiourea derivatives were designed and synthesized based on sorafenib as a lead compound. The benzimidazole moiety was traded by the pyridine ring to enhance the hydrophobic interaction and retain hydrogen bonding in the hinge region, while lipophilic moieties with different bulkiness were employed in the deep hydrophobic pocket for better hydrophobic interactions. Thiourea as a urea bioisostere was also utilized.

New phthalimide-based derivatives as EGFR-TK inhibitors: Synthesis, biological evaluation, and molecular modeling study.

A novel series of phthalimide derivatives was synthesized and evaluated for in vitro antitumor activity against six human cancer cell lines; HepG-2, HCT-116, MCF-7, Hep2, PC3 and Hela.The obtained results revealed that compound 32 was the most potent antitumor, while compounds 33, 22 and 24 showed strong activity against all tested cell lines. Further biological evaluation of the most active compounds was done and their in vitro EGFR-TK inhibition was tested, and the results came in accordance with the results of antitumor testing, where 32 displayed promising inhibitory activity (IC = 0.

Design, synthesis and biological evaluation of new series of hexahydroquinoline and fused quinoline derivatives as potent inhibitors of wild-type EGFR and mutant EGFR (L858R and T790M).

New series of hexahydroquinoline and fused quinoline derivatives were designed and synthesized. The thirty seven new compounds were screened for in vitro antitumor activity against HepG2, HCT-116 and MCF-7 cancer cells. Results indicated that compounds 2e, 2h, 5b, 5c, 6a, 7d and 9b have the strongest potency against the three cancer cells, and they were further screened for in vitro cytotoxicity against A431 and H1975 cancer cells, as well as WI38 and WISH normal cells.

New series of isoxazole derivatives targeting EGFR-TK: Synthesis, molecular modeling and antitumor evaluation.

New series of isoxazole derivatives were synthesized and evaluated for in vitro antitumor activity against HepG2, MCF-7 and HCT-116 cancer cells. Results showed that 4b and 25a are the most potent members against the three cancer cells (IC = 6.38-9.

Synthesis, in vivo anti-inflammatory, COX-1/COX-2 and 5-LOX inhibitory activities of new 2,3,4-trisubstituted thiophene derivatives.

New series of thiophene derivatives were synthesized and evaluated for their in vivo anti-inflammatory activity using carrageenan-induced paw edema model. The most active in vivo anti-inflammatory compounds 5b, 11b, 14c, 18c, 19c and 20d were further evaluated for their in vitro COX-1/COX-2 and 5-LOX inhibitory activities. The in vitro assay results revealed that the N-(4-(4-chlorophenyl)-3-cyanothiophen-2-yl)-2-morpholinoacetamide (5b) possesses the highest selectivity toward COX-2 (IC = 5.

1,4,5,6,7,8-Hexahydroquinolines and 5,6,7,8-tetrahydronaphthalenes: A new class of antitumor agents targeting the colchicine binding site of tubulin.

New series of 2-amino-1,4,5,6,7,8-hexahydroquinoline-3-carbonitriles 3a,b and 2-amino-5,6,7,8-tetrahydronaphthalene-1,3-dicarbonitriles 4a-h were synthesized and evaluated for their antitumor activity. In vitro antitumor screening of the new members against HepG2, HCT-116 and MCF-7 cancer cells showed that the tetrahydronaphthalene-1,3-dicarbonitrile 4c has the highest potency against the three tested cancer cells (IC = 6.02, 8.

Synthesis of Cyclobutane Analogue 4: Preparation of Purine and Pyrimidine Carbocyclic Nucleoside Derivatives.

The coupling of 2-bromo-3-benzoyloxycyclobutanone with purine under basic conditions produces two regioisomers consisting of the and alkylated products in equal amounts in their racemic forms. The distribution of the isomers is consistent with the charge delocalization between the and positions of the purinyl anion. The structural assignments and relative stereochemistry of each regioisomer were based on 1 and 2D NMR techniques.

Synthesis and biological screening of new thiazolo[4,5-d]pyrimidine and dithiazolo[3,2-a:5',4'-e]pyrimidinone derivatives as antimicrobial, antiquorum-sensing and antitumor agents.

New thiazolopyrimidine and dithiazolopyrimidinone derivatives 2-11 were synthesized and estimated for antimicrobial activity against S. aureus, B. cereus, E.

Microwave-assisted synthesis and antitumor evaluation of a new series of thiazolylcoumarin derivatives.

A new series of thiazolylcoumarin derivatives was synthesized. The designed strategy embraced a molecular hybridization approach which involves the combination of the thiazole and coumarin pharmacophores together. The new hybrid compounds were tested for antitumor efficacy over cervical (Hela) and kidney fibroblast (COS-7) cancer cells.

Synthesis, antimicrobial, antiquorum-sensing, antitumor and cytotoxic activities of new series of cyclopenta(hepta)[b]thiophene and fused cyclohepta[b]thiophene analogs.

New series of cyclopenta(hepta)[b]thiophene and fused cyclohepta[b]thiophene analogs were synthesized. The new analogs were assessed for antibacterial efficacy toward Escherichia coli ATCC 12435, Bacillus cereus UW 85 and Staphylococcus aureus. Compounds 5a, 6b and 12 showed eminent activity toward all selected bacterial strains compared to ampicillin.

Isatin-β-thiocarbohydrazones: Microwave-assisted synthesis, antitumor activity and structure-activity relationship.

A new series of isatin-β-thiocarbohydrazones was synthesized based on the pharmacophoric features of triapine required for metal chelation. Our strategy involved the modifications of triapine basic skeleton by replacing pyridinyl moiety with isatin which retains the tridentate feature of triapine needed for metal chelation. The new compounds were esteemed for their antitumor efficacy against cervical cancer (Hela) and kidney fibroblast cancer (COS-7) cell lines.

Synthesis, Antimicrobial, Antiquorum-Sensing, and Cytotoxic Activities of New Series of Isoindoline-1,3-dione, Pyrazolo[5,1-a]isoindole, and Pyridine Derivatives.

New series of isoindoline-1,3-diones 2-9, pyrazolo[5,1-a]isoindoles 10-14, and pyridines 16-18 were synthesized. Twenty of the synthesized compounds were screened for their antibacterial activity against S. aureus, B.

Antimicrobial and antiquorum-sensing studies. Part 3: Synthesis and biological evaluation of new series of [1,3,4]thiadiazoles and fused [1,3,4]thiadiazoles.

New series of [1,3,4]thiadiazoles and fused [1,3,4]thiadiazoles were synthesized. The newly synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus, Bacillus cereus, and Escherichia coli. Compounds 3b and 10a displayed the highest activity against E.

Synthesis and in vitro antitumor activity of new series of benzothiazole and pyrimido[2,1-b]benzothiazole derivatives.

New series of benzothiazole and pyrimido[2,1-b]benzothiazole derivatives were synthesized and characterized by analytical and spectrometrical methods (IR, HRMS, (1)H and (13)C NMR). Nineteen of the synthesized compounds were selected by the National Cancer Institute (NCI), USA, to be screened for their antitumor activity at a single dose (10 μM) against a panel of 60 cancer cell lines. The most active compounds, 4, 6, 10, 14, 17 and 20 were selected for further evaluation at five dose level screening.

Structure-based drug design and biological evaluation of 2-acetamidobenzothiazole derivative as EGFR kinase inhibitor.

EGFR tyrosine kinase has been reported mainly in 40-80% of non-small lung cancers, in addition to colon and breast cancers. In this study, we illustrate the synthesis of a highly potent antitumor agent. The synthesized compound 4 was screened at NCI, USA, for antitumor activity against non-small lung cancer, colon cancer and breast cancer cell lines.

EGFR tyrosine kinase targeted compounds: in vitro antitumor activity and molecular modeling studies of new benzothiazole and pyrimido[2,1-b]benzothiazole derivatives.

In this study, we illustrate computer aided drug design of new benzothiazole and pyrimido[2,1-b]benzothiazole derivatives as epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors. Compounds 1-5 were screened at NCI, USA, for antitumor activity against non-small cell lung cancer (NCI-H522), colon cancer (HCT-116, HCT-15 and HT29) and breast cancer (MDA-MB-468 and MDA-MB-231/ATCC) cell lines in which EGFR is overexpressed in varying levels. Results indicated that these compounds are more potent antitumor agents compared to erlotinib against HT29 and MDA-MB-231/ATCC cell lines.

Synthesis, antimicrobial, antiquorum-sensing, antitumor and cytotoxic activities of new series of fused [1,3,4]thiadiazoles.

New series of [1,3,4]thiadiazolo[3,2-a]pyrimidines, benzo[h][1,3,4]thiadiazolo[2,3-b]quinazolines, benzothiadiazolotriazocine, and imidazo[2,1-b][1,3,4]thiadiazoles have been synthesized and characterized by analytical and spectrometrical methods (IR, MS, (1)H and (13)C NMR). Twenty of the synthesized compounds were screened for antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus cereus. They were found to be either moderately active, slightly active or inactive against the tested microorganisms.