Design, Synthesis and Evaluation of 1H‐1, 2, 3‐Triazol‐4‐yl‐methyl Tethered 3‐Pyrrolylisatins as Potent Anti‐Breast Cancer Agents. Issue 19 (16th May 2018)

• Record Type: Journal Article
• Authors: Jain, Ruchi; Gahlyan, Parveen; Dwivedi, Sonam; Konwar, Rituraj; Kumar, Sudhir; Bhandari, Mamta; Arora, Ritu; Kakkar, Rita; Kumar, Rakesh; Prasad, Ashok K.
• Is Part Of: ChemistrySelect. Volume 3:Issue 19(2018)
• Page Start: 5263
• Page End: 5268
• Publication Date: 2018-05-16
• Subjects: Anti-breast Cancer Agents -- Isatin -- Molecular docking -- Pyrrole -- Triazole; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201800420
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Cancer is a class of diseases that is characterized by the uncontrollable or unstoppable growth of abnormal cells with the potential to invade or spread to other normal body parts. According to WHO estimates, globally 10 million new cancer cases are diagnosed each year. Its 100% prevention becomes a major challenge for the scientific fraternity. Therefore, there is an urgent need to discover new drugs that could overcome the present issue. In order to meet the challenges, a library of 22 novel 1H‐1, 2, 3‐triazol‐4‐yl‐methyl tethered 3‐pyrrolyl isatin derivatives have been synthesized and well characterized by using different spectral techniques. The newly synthesized conjugates were screened for their anti‐proliferative activity against breast cancer MCF‐7 and MDA‐MB‐231, as well as human embryonic HEK 293 cell lines by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide (MTT) assay. Cytotoxicity studies revealed that six of the compounds among entire series are three‐fold more potent than the commercially available reference drug tamoxifen against MDA‐MB‐231 and relatively safe towards HEK‐293 cells. In order to validate experimental results, the possible binding interaction of the most potent conjugate and tamoxifen with Topoisomerase II has been scrutinized by molecular docking studies. Abstract : The present manuscript explicated the first direct synthesis of 1 H ‐1, 2, 3‐triazol‐4‐yl‐methyl tethered 3‐pyrrolyl isatin derivatives by the coupling of 4‐hydroxyproline with 1, 2, 3‐triazole tethered isatins. Cytotoxicity studies revealed that six compounds among the entire series are three‐fold more potent than the reference drug tamoxifen against MDA‐MB‐231 and relatively safe towards HEK‐293 cells. In order to validate our experimental results, the possible binding interaction of the most potent conjugate 5 r and tamoxifen with Topo II have been scrutinized by molecular docking studies.