3‐Aminomethyl pyridine chalcone derivatives: Design, synthesis, DNA binding and cytotoxic studies. (18th May 2018)

• Record Type: Journal Article
• Authors: Durgapal, Sunil Dutt; Soni, Rina; Umar, Shweta; Suresh, Balakrishnan; Soman, Shubhangi S.
• Is Part Of: Chemical biology & drug design. Volume 92:Number 1(2018)
• Page Start: 1279
• Page End: 1287
• Publication Date: 2018-05-18
• Subjects: aminomethyl pyridine -- anticancer activity -- chalcone derivatives -- cytotoxic studies -- DNA binding; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.13189
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract : Herein we report design, synthesis, and anticancer activity of compounds6a–h and11a–j . Compounds6a–f were designed based on 3‐aminomethyl pyridine attached to different acetamide derivatives and in compounds6g–h it was attached to coumarin moiety. Coumarin containing compounds6g–h showed very poor anticancer activity against both A549 (Lungs cancer cell line), and MCF‐7 (Breast cancer cell line) cell lines in MTT assay. Compounds11a–j were designed as derivatives of 3‐aminomethyl pyridine and 4‐amino chalcones. A series of chalcone derivatives of 3‐aminomethyl pyridine11a–j have been synthesized and screened for their in vitro anticancer activity and DNA binding affinity. Most of the compounds showed very good antimitotic activity against A549 cell line as compared to fluorouracil. Compounds11g and11i were selected for DNA‐binding studies as they showed excellent activity against cancer cell lines in MTT assay. CT‐DNA binding affinity of compounds11g and11i have been investigated by UV based DNA titration and fluorescence emission study against DNA‐EtBr complex. Interestingly, compound11i has displayed excellent antiproliferative activity, with IC50 0.0067 ± 0.0002 μm, against MCF‐7 cell line. Compound11i has been studied for its cytotoxicity using MTT, LDH, as well as EtBr/AO assay and was found to induce apoptosis in the cancerous cell line. Abstract : Aminopyridine chalcone derivatives11a–11j were screened for their potency utilizing an MTT assay. Compound11i showed excellent IC50 value of 0.245 µm and 0.0067 µm in A549 and MCF7 cell lines respectively. DNA binding of compound11g and11i showed intercalation with CT‐DNA. The cytotoxic studies of compound11i have shown apoptosis in MCF‐7 cell line.