RESUMO
Curcumin, a natural diaryl heptanoid continues to be used as an alternative medicinal agent in many parts of South East Asia for treatment of many ailments. It can be usually obtained from substituted aryl aldehydes and acetylacetone and this route enables synthesis of a diverse set of curcumin analogues. Numerous analogues have been synthesized and tested by several researchers to investigate their activity against known biological targets and to improve upon the pharmacological and ADME profile by modifying substitutions on aromatic rings, ß-diketone moiety and two flanking double bonds conjugated to the ß-diketone moiety. Successful synthesis of such derivatives with modifications has resulted in the development of potential anticancer candidates that target various stages in cancer cell growth and development. Based on the evidences in modifications of these three functional elements, we have attempted to summarize the structure activity relationship of molecules which can be further utilized by researchers in medicinal chemistry in exploring the structure of curcumin.
Assuntos
Antineoplásicos/química , Curcumina/análogos & derivados , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Curcumina/síntese química , Curcumina/toxicidade , Humanos , Cetonas/química , Relação Estrutura-AtividadeRESUMO
A series of novel isoxazolo[5',4':5,6]pyrido[2,3-b]indoles 7a-h were synthesized and tested for their in vitro and in vivo anticancer activities. The analogs 7d and 7g have shown potential anticancer activity as compared with the reference compound Cisplatin.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Indóis/síntese química , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Humanos , Indóis/química , Indóis/farmacologia , Concentração Inibidora 50 , Isoxazóis/síntese química , Isoxazóis/química , Isoxazóis/farmacologia , Masculino , Camundongos , Estrutura Molecular , Piridonas/síntese química , Piridonas/química , Piridonas/farmacologiaRESUMO
A series of novel 8/10-trifluoromethyl-substituted-imidazo[1,2-c] quinazolines have been synthesized and evaluated in vivo (rat paw edema) for their anti-inflammatory activity and in silico (docking studies) to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzymes (COX-1 and COX-2) employing GOLD (CCDC, 4.0.1 version) software. The compounds, 9b and 10b, were found to have good anti-inflammatory activity [around 80% of the standard: indomethacin]. The binding mode of the title compounds has been proposed based on the docking studies.
Assuntos
Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Flúor/química , Quinazolinas/síntese química , Quinazolinas/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Ratos , Ratos WistarRESUMO
A series of novel pyrimido[1,2-b]indazoles 5, 7 have been prepared from 3-trifluoromethyl-5-phenyl-2,6-dicyano anilines 1 via novel indazole regioisomers 3 and 4 through a facile strategy. Specific examples were evaluated for anticancer activity in vitro and found to exhibit promising activity against A-549 cell lines and are more effective than Etoposide. QSAR models were developed and validated by cross-validation method. The results of the best QSAR model were further compared with the crystal structure of tubulin protein. The binding energies estimated were found to have a good correlation with the experimental inhibitory potencies.
