title: Synthesis and screening of ursolic acid-benzylidine derivatives as potential anti-cancer agents.
abstract: Ursolic acid present abundantly in plant kingdom is a well-known compound with various promising biological activities including, anti-cancer, anti-inflammatory, hepatoprotective, antiallergic and anti-HIV properties. Herein, a library of ursolic acid-benzylidine derivatives have been designed and synthesized using Claisen Schmidt condensation of ursolic acid with various aromatic aldehydes in an attempt to develop potent antitumor agents. The compounds were evaluated against a panel of four human carcinoma cell lines including, A-549 (lung), MCF-7 (breast), HCT-116 (colon), THP-1 (leukemia) and a normal human epithelial cell line (FR-2). The results from MTT assay revealed that all the compounds displayed high level of antitumor activities compared with the triazole analogs (previously reported) and the parent ursolic acid. However, compound 3b, the most active derivative was subjected to mechanistic studies to understand the underlying mechanism. The results revealed that compound 3b induced apoptosis in HCT-116 cell lines, arrest cell cycle in the G1 phase, caused accumulation of cytochrome c in the cytosol and increased the expression levels of caspase-9 and caspase-3 proteins. Therefore, compound 3b induces apoptosis in HCT-116 cells through mitochondrial pathway.
authors: Department of Chemistry, University of Kashmir, Srinagar, 190006, India.
authors: Bilal Ahmad
authors: BA
authors: Dar
authors: Department of Chemistry, University of Kashmir, Srinagar, 190006, India. Electronic address: loneali33@gmail.com.
authors: Ali Mohd
authors: AM
authors: Lone
authors: Department of Chemistry, University of Kashmir, Srinagar, 190006, India.
authors: Wajaht Amin
authors: WA
authors: Shah
authors: Department of Chemistry, University of Kashmir, Srinagar, 190006, India.
authors: Mushtaq Ahmad
authors: MA
authors: Qurishi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: Aromatic aldehydes; Benzylidine; Claisen Schmidt condensation; Cytotoxic activity; Ursolic acid