ABSTRACT
A series of novel 1,2,3-triazole-pyrimidine-urea hybrids were designed, synthesized and evaluated for anticancer activity against four selected cancer cell lines (MGC-803, EC-109, MCF-7 and B16-F10). Majority of the synthesized compounds exhibited moderate to potent activity against all the cancer cell lines assayed. Particularly, compounds 26, 30 and 38 exhibited excellent growth inhibition against B16-F10 with IC50 values of 32nM, 35nM and 42nM, respectively. Flow cytometry analysis demonstrated that compound 26 induced the cellular apoptosis in a concentration-dependent manner.
Subject(s)
Antineoplastic Agents/chemistry , Drug Design , Pyrimidines/chemistry , Triazoles/chemistry , Urea/analogs & derivatives , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Pyrimidines/chemical synthesis , Pyrimidines/pharmacology , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/pharmacology , Urea/chemical synthesis , Urea/pharmacologyABSTRACT
Three series of novel AHL analogs were synthesized and evaluated for their in vitro cytotoxic activity against four human cancer cell lines. The SARs investigation indicated that AHLs with a terminal phenyl group, especially those with the chalcone scaffold had remarkably enhanced cytotoxicity than those with the hydrophobic side chains. Besides, some of these compounds were much more potent than 5-Fu and natural OdDHL. Through the detailed SARs discussions, we found that compounds 10a-k and 14 with the 4-amino chalcone scaffold showed excellent inhibition against all the tested cancer cell lines and were much more potent than 5-Fu and AHLs. Such scaffold may act as a template for further lead optimization. Compound 10i with a 3, 4, 5-trimethoxy group was the most potent one against all the tested cancer cell lines. Flow cytometry analysis indicated that analog 11e induced the cellular apoptosis and cell cycle arrest of MCF-7 cells at G2/M phase in a concentration-and time-dependent manner.
Subject(s)
Acyl-Butyrolactones/chemistry , Acyl-Butyrolactones/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Design , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Proliferation/drug effects , Chalcone/chemistry , Humans , Inhibitory Concentration 50 , MCF-7 Cells , Structure-Activity RelationshipABSTRACT
A series of novel 1,2,3-triazole-pyrimidine hybrids were designed, synthesized and evaluated for their anticancer activity against four selected cancer cell lines (MGC-803, EC-109, MCF-7 and B16-F10). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Compound 17 showed the most excellent anticancer activity with single-digit micromolar IC50 values ranging from 1.42 to 6.52 µM. Further mechanism studies revealed that compound 17 could obviously inhibit the proliferation of EC-109 cancer cells by inducing apoptosis and arresting the cell cycle at G2/M phase.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Pyrimidines/pharmacology , Triazoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Molecular Structure , Pyrimidines/chemistry , Structure-Activity Relationship , Triazoles/chemistryABSTRACT
Trying to develop potent and selective anticancer agents, two series of novel 1,2,4-triazolo[3,4-a]phthalazine derivatives were designed and synthesized. Their antitumor activities were evaluated by MTT method against four selected human cancer cell lines (MGC-803, EC-9706, HeLa and MCF-7). Our results showed that compound 11h exhibited good anticancer activities compared to 5-fluorouracil against the four tested cell lines, with IC50 values ranging from 2.0 to 4.5 µM. Flow cytometry analysis indicated that compound 11h induced the cellular early apoptosis and cell cycle arrest at G2/M phase in EC-9706.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Design , Phthalazines/chemistry , Phthalazines/pharmacology , Triazoles/chemistry , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Chemistry Techniques, Synthetic , Drug Screening Assays, Antitumor , Humans , Phthalazines/chemical synthesisABSTRACT
A series of pyrimidine-benzimidazol hybrids was synthesized and evaluated for anticancer activity on four human cancer cell lines including MCF-7, MGC-803, EC-9706 and SMMC-7721. Some of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 5a-b and 6a-b showed most effective activity. Compounds 5b and 6b were more cytotoxic than 5-fluorouracil against all tested four human cancer cell lines, with IC50 values ranging from 2.03 to 10.55 µM and 1.06 to 12.89 µM, respectively. Flow cytometry analysis demonstrated that treatment of MGC-803 with 6b led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death.
Subject(s)
Antineoplastic Agents/pharmacology , Benzimidazoles/pharmacology , Pyrimidines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Benzimidazoles/chemistry , Cell Cycle/drug effects , Cell Death/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Molecular Structure , Pyrimidines/chemistry , Structure-Activity RelationshipABSTRACT
A series of novel 4-substituted-2-{[(1H-benzo[d]imidazol-2-yl)methyl] thio}-6-methylpyrimidine derivatives were designed, synthesized and evaluated for their cytotoxic activities against four human cancer cell lines and inhibitory activities against five type culture strains in vitro. Some of synthetic pyrimidine-benzimidazol combinations showed good inhibitory activities against Stenotrophomonas maltophilia, especially compounds 7b and 7c. Compounds 7a and 7d exhibited enhanced activities against MGC-803 in vitro, when compared to 5-Fu.
Subject(s)
Benzimidazoles/chemical synthesis , Benzimidazoles/pharmacology , Pyrimidines/chemical synthesis , Pyrimidines/pharmacology , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Bacteria/drug effects , Benzimidazoles/chemistry , Candida albicans/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Combinatorial Chemistry Techniques , Humans , Inhibitory Concentration 50 , Microbial Sensitivity Tests , Molecular Structure , Pyrimidines/chemistryABSTRACT
A series of novel 1,2,4-triazolo [3,4-a] phthalazine derivatives were synthesized in five steps from a common precursor, phthalic anhydride. Most of synthesized phthalazine derivatives showed inhibitory activity against Staphylococcus aureus. One of phthalazine derivatives 5l showed inhibitory activity against all tested bacterial and fungal strains.