Design, synthesis, and biological evaluation of N-(4-substituted)-3-phenylisoxazolo[5,4-d]pyrimidin-4-amine derivatives as apoptosis-inducing cytotoxi...
Basic Information
ID: ALA4823299
Journal: Bioorg Med Chem Lett
Title: Design, synthesis, and biological evaluation of N-(4-substituted)-3-phenylisoxazolo[5,4-d]pyrimidin-4-amine derivatives as apoptosis-inducing cytotoxic agents.
Authors: Gaikwad NB, Bansod S, Mara A, Garise R, Srinivas N, Godugu C, Yaddanapudi VM.
Abstract: A library of new 3-phenylisoxazolo[5,4-d]pyrimidines (8-10) was designed based on a scaffold hybridization technique incorporating the important pharmacophoric features of 4-aminopyrimidine and phenyl isoxazole scaffold which is renowned for its BET inhibition activity. The designed molecules were synthesized and evaluated with the NCI-60 cell line panel. Examination by NCI-60 cell lines at single-dose and the five-dose study showed that compound 10h exhibited promising growth inhibitory effects with GI50 values on various cancer cell lines such as HCT-15 (Colon Cancer)-0.0221 μM, MDA-MB-435 (Melanoma) - 0.0318 μM, SNB-75(CNS Cancer)-0.0263 μM, and MCF7 (Breast Cancer)-0.0372 μM. Further studies to know the mechanism of action of 10h based on the phase-contrast microscopic evaluation, DAPI, acridine orange/ethidium bromide (AO/EB) staining, and annexin V-FITC assays revealed that elevation in the intracellular ROS leads to alteration in mitochondrial membrane potential which in turn induced the apoptosis in BT-474 cancer cells, which could be the plausible mechanism of action for compound 10h.
CiteXplore: 34333139
DOI: 10.1016/j.bmcl.2021.128294
Patent ID: ┄