Synthesis of imidazothiadiazole–benzimidazole conjugates as mitochondrial apoptosis inducers

Autor:	Ahmed Kamal, V. Lakshma Nayak, M.V.P.S. Vishnuvardhan, M. P. Narasimha Rao, Swapna Ponnampalli, Bagul Chandrakant, Kishore Mullagiri
Rok vydání:	2014
Předmět:	Pharmacology Programmed cell death Organic Chemistry Pharmaceutical Science Cell cycle Biology Biochemistry Molecular biology Mechanism of action Cell culture Annexin Apoptosis Drug Discovery medicine Molecular Medicine Cytotoxic T cell DNA fragmentation medicine.symptom
Zdroj:	Med. Chem. Commun.. 5:1644-1650
ISSN:	2040-2511 2040-2503
Popis:	A series of imidazothiadiazole–benzimidazole conjugates (3a–z) were synthesized and evaluated for their cytotoxic activity against a set of four selected human cancer cell lines. Amongst them, compounds 3b and 3y exhibited significant antiproliferative activity in ME-180 (cervical) cell line. Flow cytometric analysis showed that these two compounds arrested the cell cycle in the G0/G1 phase leading to the loss of mitochondrial membrane potential followed by apoptotic cell death. Further, Hoechst 33258 staining, DNA fragmentation assay, Annexin V staining assay and caspase-3 also suggested that 3b and 3y induced cell death by apoptosis. Docking studies revealed that compound 3b binds to the Gly142, Phe101, Asn140 and Arg143 on B-cell lymphoma 2 (Bcl-2) proteins and inhibition of Bcl-2 protein could be the possible mechanism of action for these compounds.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::3296d5af4ea8211aa05e0272cb57f95f https://doi.org/10.1039/c4md00219a Zobrazit plný text záznamu