ABSTRACT
A series of novel pyrido[2,3-d]pyrimidine derivatives 6 were prepared starting from 2-amino-3-cyano-4-trifluoromethyl-6-phenyl pyridine 3 via Grignard's reaction, cyclization followed by coupling with aliphatic and cyclic amines. All the compounds 6 were screened for antibacterial, minimum bactericidal concentration (MBC), biofilm inhibition activity as well as antifungal and minimum fungicidal concentration (MFC) activities. Among the screened compounds, the compounds 6e, 6f, and 6m which showed exhibiting promising activity have been identified. The results reveal that the compound pyrido[2,3-d]pyrimidine derivative 6e altered the sterol profile which may exert its antifungal activity through inhibition of ergosterol biosynthesis and could be an ideal candidate for antifungal therapy. The molecular docking results also validated the antifungal results.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Fungicides, Industrial/pharmacology , Molecular Docking Simulation , Pyrimidines/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Bacillus subtilis/drug effects , Dose-Response Relationship, Drug , Escherichia coli/drug effects , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Klebsiella/drug effects , Microbial Sensitivity Tests , Micrococcus luteus/drug effects , Molecular Structure , Pseudomonas aeruginosa/drug effects , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Staphylococcus aureus/drug effects , Structure-Activity RelationshipABSTRACT
A series of novel 1,2,3-triazole substituted N-phenyl nitrone derivatives 5a-e were prepared in three steps starting from 1-substituted-1,2,3-triazole-4-carbaldehydes 2 via Schiff's base formation, reduction followed by oxidation. Similarly, 1,2,3-triazole substituted N-alkyl nitrone derivatives 6a-p were prepared in single step starting from compound 2 on reaction with N-alkyl hydroxylamine hydrochlorides. All the final compounds were screened for anti-inflammatory and anticancer activity against various cancer cell lines. Among the compounds tested, the compounds 5a, 5d, 6a, 6b, 6m and 6o exhibited significant inhibition of IL-1ß secretion as a measure of anti-inflammatory activity. Compound 5b, 5c, 6h, 6i and 6o exhibited significant activity against all the cell lines (A549, COLO 205, MDA-MB 231 and PC-3) at IC50 values of <15 µM.
Subject(s)
Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Nitrogen Oxides/chemistry , Nitrogen Oxides/pharmacology , Triazoles/chemistry , Anti-Inflammatory Agents/chemical synthesis , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Cell Survival/drug effects , Chemistry Techniques, Synthetic , Humans , Inhibitory Concentration 50 , Nitrogen Oxides/chemical synthesisABSTRACT
The propargyl alcohol on reaction with aldoxime and NaOCl in DCM gave exclusively (3-arylisoxazol-5-yl) methanol 1. The compound 1 was oxidized to an aldehyde 2 followed by reaction with aniline resulted in Schiff's base 3. The compounds 3 were further reacted with various aldehydes having α-hydrogen using molecular iodine as catalyst and which yielded 5-(3-alkylquinolin-2-yl)-3-aryl isoxazole derivatives 4. All the final compounds 4 were screened against four human cancer cell lines (A549, COLO 205, MDA-MB 231 and PC-3) and among these compounds 4n showed potent cytotoxicity against all the cell lines at IC50 values of <12 µM.
Subject(s)
Antineoplastic Agents/chemical synthesis , Isoxazoles/chemistry , Quinolines/chemistry , Aniline Compounds/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Cell Line, Tumor , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Isoxazoles/chemical synthesis , Isoxazoles/toxicity , Schiff Bases/chemistryABSTRACT
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.
