ABSTRACT
The newly synthesized pyrido[2,3-a]carbazoles were prepared in good yields by multicomponent reactions under L-proline as promoter and structurally characterized. Few compounds showed significant activity toward both gram-positive, gram-negative bacterial strains. All compounds exerted negative efficacy for antifungal activity except compounds 5f and 7f which showed moderate activity. All compounds showed weak to moderate capacity for scavenging DPPH. The cytotoxicity was evaluated by Sulforhodamine B assay against A-549, B16F10, HCT-15, SKMel2 and SKOV3 cell lines and compared with standard drug cisplatin. Compound 5f outperformed cisplatin against A-549, HCT-15, SKMel2 and B16F10 cell lines. Compound 5e outranged cisplatin against A-549, HCT-15, and SKMel2 cell lines. 5b outperformed cisplatin specifically against B16F10. The preliminary structure activity relationships were carried out.
Subject(s)
Carbazoles/chemical synthesis , Carbazoles/pharmacology , Chemistry Techniques, Synthetic/methods , Drug Design , Proline/chemistry , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Bacteria/drug effects , Carbazoles/chemistry , Cell Line, Tumor , Free Radical Scavengers/chemical synthesis , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Fungi/drug effects , Humans , Inhibitory Concentration 50 , Microbial Sensitivity Tests , Models, Molecular , Molecular Conformation , Structure-Activity RelationshipABSTRACT
Bioassay-directed fractionation of a methanolic extract from the seeds of Draba nemorosa (Brassicaceae) led to isolation of a new flavonol glycoside, drabanemoroside (5, kaempferol 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranose) along with four known flavonoid derivatives (1-4), four cardenolide glycosides (6-9). Kaempferol glycosides 2 and 5 showed strong cytotoxicity against human small lung cancer cell line A549 and melanoma SK-Mel-2 with an IC(50) of 0.5 microg/mL and 1.9 microg/mL, respectively. Cardenolide glycosides 6-9 showed potent cytotoxicity (A549) in the range of 0.01-0.032 microg/mL. Their structures were characterized based on spectroscopic data (2D NMR, HRTOFMS, IR, and UV) and comparison of literature values. The carbohydrate units were also confirmed by comparing the hydrolysate of 5 with authentic monosaccharides.
