RESUMO
2-Halogenatedphenyl benzoxazole-5-carboxylic acids with mono-halogen (chloro, bromo and fluoro) substituted at ortho-, meta- and para-positions on the phenyl ring were designed and synthesized based on significance of presence of halogen in increasing number of marketed halogenated drugs and importance of benzoxazoles. These 2-alogenatedphenylbenzoxazole-5-carboxylic acids and their methyl esters were screened for anti-inflammatory activity, and cytotoxicity. 2-(3-Chlorophenyl)benzoxaole-5-carboxylic acid (6b) exhibited significant anti-inflammatory activity with IC50 values of 0.103â mM almost equivalent to the standard drug ibuprofen (0.101â mM). 2-(4-Chlorophenyl)benzoxaole-5-carboxylic acid (6c) showed excellent cytotoxic activity against 22Rv1 cells (human prostate carcinoma epithelial cell lines) with IC50 value of 1.54â µM better than that of standard drug doxorubicin having IC50 value of 2.32â µM. More importantly, the selectivity index of this potential molecule was found to be 57.74. Molecular docking analysis resulted in good binding interactions of these compounds with their respective biochemical targets viz. Cyclooxygenase-2 and aldo-keto reductase IC3.
Assuntos
Antineoplásicos , Benzoxazóis , Humanos , Simulação de Acoplamento Molecular , Benzoxazóis/farmacologia , Benzoxazóis/química , Ciclo-Oxigenase 2/metabolismo , Ibuprofeno , Citotoxinas , Ácidos Carboxílicos/farmacologia , Relação Estrutura-Atividade , Antineoplásicos/química , Anti-Inflamatórios/farmacologia , Doxorrubicina , Aldo-Ceto Redutases/metabolismo , Estrutura MolecularRESUMO
Nineteen heterocyclic chalcones were synthesized from 4-acetyl-5-methylquinolylpyrazole and heteroaryl (imidazole, pyrazole, thiophene, indole and triazole) aldehydes and were screened inâ vitro using four tumor cell lines for their cytotoxic capability and for antimicrobial activity. The chalcone 5b exhibited the highest activity with IC50 values 2.14â µM against colon (HCT-116) and 5.0â µM, against prostate (PC-3) cancer cell lines and also displayed good activity against fungal strain (A.â niger) with MIC value 9.1â µM. The chalcones 5q and 5p displayed good activity against bacterial strains (S.â aureus) having MIC value 2.6â µM and fungal strain (C.â albicans) having MIC value 5.4â µM, respectively. The molecular docking outcome revealed that the synthesized heterocyclic chalcones demonstrated hydrogen bond, hydrophobic and electrostatic interactions with their respective biochemical targets.