P. Nagender

Synthesis, cytotoxicity, antimicrobial and anti-biofilm activities of novel pyrazolo[3,4-b]pyridine and pyrimidine functionalized 1,2,3-triazole derivatives

A series of novel pyrazolo[3,4-b]pyridine and pyrimidine functionalized 1,2,3-triazole derivatives 8a-g and 9a-g were prepared starting from 6-trifluoromethylpyridine-2(1H)one 2 via selective O-alkylation, followed by cyclisation using hydrazine hydrate to obtain 6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-3-amine 4. Compound 4 was diazotized followed by reaction with sodium azide, resulted in 3-azido-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine 5. Compound 5 was further cyclized with N-/O-propargylated pyrimidine derivatives under Sharpless conditions and obtained compounds 6 and 7, respectively. Each set of compounds 6 and 7 were alkylated with different alkyl halides and obtained respective products 8 and 9. All the products were screened for cytotoxicity against four human cancer cell lines such as A549-Lung (CCL-185), MCF7-Breast (HTB-22), DU145-Prostate (HTB-81) and HeLa-Cervical (CCL-2), compounds 9d, 9e and 9f which showed promising activity have been identified. The products were also screened for antimicrobial, anti bio-film and MBC activities. Promising compounds in each case have been identified.

A facile strategy for the synthesis of highly substituted imidazole using tetrabutyl ammoniumbromide as catalyst

A simple and facile strategy for the synthesis of highly substituted imidazoles has been developed by multi-component condensation of 1,2-diketone, aldehyde, amine, and ammonium acetate in presence of tetrabutyl ammonium bromide as catalyst.

Synthesis of novel hydrazone and azole functionalized pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents

A series of novel pyrazolo[3,4-b]pyridine based target compounds were synthesized starting from the key intermediate ethyl 2-(3-amino-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetate 5 on reaction with hydrazine hydrate followed by reaction with different aldehydes, acid chlorides and isothiocyanates to form hydrazones 7, oxadiazoles 8, 1,2,4 triazoles 10 and thiadiazoles 11 respectively in high yield. All the final compounds were screened for anticancer activity against four human cancer cell lines. Among them, 1,2,4 triazole derivatives showed promising activity and compound 10d is identified as a lead molecule.

Synthesis of novel nicotinohydrazide and (1,3,4-oxadiazol-2-yl)-6-(trifluoromethyl)pyridine derivatives as potential anticancer agents

A series of novel nicotinohydrazide derivatives 6a-g and 1,3,4-oxadiazole functionalized pyridine derivatives 7a-k and 8a-d were prepared in series of steps. All the compounds were screened for cytotoxicity against HeLa (cervical), DU145 (prostate), HepG2 (liver) and MBA-MB-231 (breast) human cancer cell lines. Compounds 6h, 6i, 7d, 7h, 7i and 8b which showed promising cytotoxicity at <15μM concentration have been identified. Further optimization of the structure is underway to identify a lead compound.

Studies on Synthesis of Novel Triazolalkyl Tagged Trifluoromethyl Substituted Pyrimidine Derivatives and their Evaluation for Cytotoxic Activity

The 2-amino-6-trifluoromethyl-3H-pyrimidin-4-one 1 was propargylated to give two regioisomers 2, 3 in defi- nite proportions. Both regioisomers 2 and 3 were independently reacted with alkyl, aryl or cycloalkyl substituted azides under Sharpless conditions and were obtained exclusively 1,4-disubstituted triazole tagged trifluoromethyl substituted pyrimidine derivatives 4 and 5 respectively. All the final products were evaluated for cytotoxic activity against four can- cer cell lines and promising compounds were identified.