Synthesis of novel 1,2,3-triazole/isoxazole functionalized 2H-Chromene derivatives and their cytotoxic activity.

A series of novel 2-(1,2,3-triazolylmethoxy) 5a-q and isoxazole tagged 6a-g 2H-Chromene derivatives were prepared starting from salicylaldehyde and ethyl-4,4,4-trifluoroacetoacetate via cyclization to form ethyl 2-hydroxy-2-(trifluoromethyl)-2H-Chromene-3-carboxylate 3. Compound 3 on reaction with propargyl bromide resulted compound 4 and was independently reacted with aryl/alkyl azides and aryl aldoximes obtained 2-(1,2,3-triazolylmethoxy) and isoxazole tagged 2H-Chromene derivatives 5a-q, 6a-i, respectively. Compounds 6 were further hydrolysed to acid derivatives 7a-g. All the products 5a-q, 6a-i, 7a-g were screened for cytotoxic activity against four human cancer cell lines and among all the compounds, 5f, 5g, 5l, 5q showed promising activity at <20 µM concentration.

Emergence of pyrido quinoxalines as new family of antimalarial agents.

A series of novel N-alkyl dihydro pyrido quinoxaline derivatives were synthesized using Gould-Jacobs reaction and evaluated their antimalarial activity in vitro against chloroquine sensitive (3D7) and drug resistant (Dd2) strains of Plasmodium falciparum. Among the compounds tested, 10 compounds were more potent than their structural standard analog ciprofloxacin, including 2 derivatives 5e and 5h, which showed 3.3-7.4 times more potency than ciprofloxacin against both the parasite strains. The results are encouraging and a lead molecule may emerge which is useful alone or in combination therapy.

Synthesis of novel 2-alkyl triazole-3-alkyl substituted quinoline derivatives and their cytotoxic activity.

The propargyl alcohol on reaction with alkylazides under Sharpless conditions through click chemistry concept gave exclusively 1,4-disubstituted triazoles 2. The compounds 2 were oxidized to aldehydes 3 followed by reaction with aniline resulted Schiff's bases 4. The compounds 4 was further reacted with various aldehydes having α-hydrogen using molecular iodine as a catalyst and obtained 2-alkyl triazole-3-alkyl substituted quinoline derivatives 5. All the final compounds were screened against four human cancer cell lines (THP-1, Colo205, U937 & HeLa) and promising compounds have been identified.

Synthesis of novel alkyltriazole tagged pyrido[2,3-d]pyrimidine derivatives and their anticancer activity.

A series of novel alkyltriazole tagged pyrido[2,3-d]pyrimidine derivatives 5 and 6 was prepared starting from 2,3-active functional pyridine 1via cyclization, propargylation followed by reaction with alkyl or perfluoroalkyl azides under Sharpless conditions. All the compounds 5 and 6 were screened for anticancer activity against three cancer cell lines such as U(937), THP-1 and Colo205. The promising compounds 5b and 5e have been identified.

Synthesis of new 2-substituted pyrido[2,3-d]pyrimidin-4(1H)-ones and their antibacterial activity.

2-Substituted-5,7-dimethyl pyrido[2,3-d]pyrimidin-4(1H)-ones (8) were synthesized by oxidation of 2-substituted-5,7-dimethyl dihydropyrido[2,3-d]pyrimidin-4(1H)-ones (7) which were in turn prepared from 2-amino-4,6-dimethyl nicotinamide (5) and substituted aryl aldehydes (6). 2-Amino-4,6-dimethyl nicotinamide (5) was prepared from ethyl cyanoacetate (1) via malonamamidine hydrochloride (3). The compounds were characterized by IR, NMR, MS and elemental analyses. Compounds 7 and 8 were screened for antibacterial activity against gram positive and gram negative bacteria. Dehydrogenated compounds (8) showed less antibacterial activity than the compounds 7. Among all the test compounds screened for antibacterial activity 7c (1.25 microg/ml) showed greater activity. All the synthesized compounds were found inactive when screened for antifungal activity at the concentration of 200 microg/ml.

Convenient synthesis of novel 4-substitutedamino-5-trifluoromethyl-2,7-disubstituted pyrido[2,3-d] pyrimidines and their antibacterial activity.

Novel pyrido[2,3-d]pyrimidines 4 have been synthesised starting from 2-amino-4-trifluoromethyl-6-substituted nicotinonitriles 1 via imine formation, selective amination followed by Dimroth rearrangement. Compounds 4 were screened against Gram +ve and -ve bacteria in vitro. Compounds 4h and 4d showed significant activity against all species of Gram positive bacteria and moderate activity against Gram negative bacteria. N-2,4 difluorophenyl compounds 4l and 4m were the least active among all the compounds. All the compounds were inactive against Pseudomonas aeruginosa at the maximum concentration of 200 microg ml(-1).