RESUMO
Epoxyazadiradione (1), a major compound derived from Neem oil, showed modest anti-plasmodial activity against CQ-resistant and CQ-sensitive strains of the most virulent human malaria parasite P. falciparum. A series of analogues were synthesized by modification of the key structural moieties of this high yield natural product. Out of the library of all compounds tested, compounds 3c and 3g have showed modest anti-plasmodial activity against CQ-sensitive (IC50 2.8 ± 0.29 µM and 1.5 ± 0.01 µM) and CQ-resistant strains (IC50 1.3 ± 1.08 µM and 1.2 ± 0.14), while compounds 3k, 3l and 3m showed modest activity against CQ-sensitive strain of P. falciparum with IC50 values of 2.3 ± 0.4 µM, 2.9 ± 0.1 µM and 1.7 ± 0.06 µM, respectively. Additionally, cytotoxic properties of these derivatives against SIHA, PANC 1, MDA-MB-231, and IMR-3 cancer cell lines were also studied and the results indicated that low cytotoxic potentials of all the derivatives which indicating the high selectivity index of the compounds.
Assuntos
Antimaláricos/química , Antimaláricos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Azadirachta/química , Limoninas/química , Limoninas/farmacologia , Animais , Antimaláricos/síntese química , Antimaláricos/isolamento & purificação , Antineoplásicos/síntese química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Limoninas/síntese química , Limoninas/isolamento & purificação , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacosRESUMO
As part of pharmacological-phytochemical integrated studies on medicinal plants from Indian flora, costunolide (1) and dehydrocostus lactone (2), were isolated as major phytochemicals from Saussurea lappa, a plant traditionally used in different Asian systems of medicine. A series of 1,4-disubstituted-1,2,3-triazoles conjugates were synthesized through diastereo selective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reactions. All these triazolyl derivatives (5a-5j) & (7a-7j) were well characterized using modern spectroscopic techniques and evaluated for their anticancer activity against a panel of five human cancerous celllines. The results indicated that all the analogs displayed moderate cytotoxic activity.