Niacin esters of chalcones with tumor-selective properties. (1st November 2016)

• Record Type: Journal Article
• Authors: Panda, Atulya K.; Das, Umashankar; Roayapalley, Praveen K.; Sakagami, Hiroshi; Kawase, Masami; Balzarini, Jan; De Clercq, Erik; Dimmock, Jonathan R.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31:Number 6(2016:Dec.)
• Page Start: 1451
• Page End: 1456
• Publication Date: 2016-11-01
• Subjects: Chalcones -- cytotoxicity -- niacin -- QSAR -- tumor-specific toxicity -- unsaturated ketones; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2016.1144595
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Novel series of niacin esters of chalcones2, 4 and6 were designed as antineoplastic agents that have the potential to release the chemoprotectant niacin. These enones are cytotoxic to human CD4 + T-lymphocyte Molt 4/C8 and CEM and murine leukemia L1210 cells. Quantitative structure–activity relationship (QSAR) studies of the biodata in series4 revealed that cytotoxic potency was enhanced by placing electron-repelling groups in one of the aryl rings. The compounds are lethal to HL-60, HSC-2, HSC-3 and HSC-4 neoplasms but less toxic to nonmalignant hepatocyte growth factor, hematopoietic progenitor cell and human periodontal ligament fibroblast cells. Hence, the compounds display tumor-selective toxicity. These chalcones are well tolerated in mice and no overt toxicity was noted. The results establish that in general the compounds in series2, 4 and6 have positive characteristics which warrant further studies.