Synthesis and evaluation of N-(4-(substituted)-3-(trifluoromethyl) phenyl) isobutyramides and their N-ethyl analogous as anticancer,anti-angiogenic & antioxidant agents: In vitro and in silico analysis |
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| Institution: | 1. School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Nanded-431 606, MS, India;2. Gramin Science (Vocational) College, Vishnupuri, Nanded-431 606, MS, India;3. DD Bhoyar College of Arts and Science Mouda, Nagpur, 441104, MS, India;4. Bioinformatics Centre, Savitribai Phule Pune University, Pune, 411007, India;5. Organic Chemistry Research Laboratory, Department of Chemistry, Institute of Science, Nagpur, MS, India;6. Department of Biotechnology, Savitribai Phule Pune University, Pune, 411007, MS, India;1. Department of Computer Science & Engineering, Dr. Sudhir Chandra Sur Degree Engineering College, 540, Dum Dum Road, Near Dum Dum Jn. Station, Surermath, Kolkata, 700074, India;2. Department of Computer Science & Engineering, University of Calcutta, Saltlake City, Kolkata, 700073, India;3. Department of Computer Science & Engineering, Netaji Subhash Engineering College, Techno City, Panchpota, Garia, Kolkata, 700152, India;1. Department of Pharmacy, Cangzhou Central Hospital, Hebei Medical University, Cangzhou 061014, China;2. Cangzhou Institute for Food and Drug Control, Cangzhou 061003, China;1. Hainan Key Laboratory for Computational Science and Application, Hainan Normal University, Haikou 571158, China;2. Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610054, China;3. Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou 324000, China;1. Hainan Key Laboratory for Computational Science and Application, Hainan Normal University, Haikou 571158, China;2. Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610054, China;3. Yangtze Delta Region Institute (Quzhou), Universityof Electronic Science and Technology of China, Quzhou 324000, China;1. School of Electronic and Communication Engineering, Shenzhen Polytechnic, Shenzhen, 518000, China;2. School of Management, Shenzhen Polytechnic, Shenzhen, 518000, China |
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| Abstract: | N-(4-(substituted)-3-(trifluoromethyl) phenyl) isobutyramides and their N-ethyl analogues (flutamides) are versatile scaffolds with a wide spectrum of biological activities. A series of new N-(4-(substituted)-3-(trifluoromethyl) phenyl) isobutyramides (8a-t) and their N-ethyl analogous (9a-t) were synthesized and characterized. The inhibitory potential of the synthesized compounds on the viability of three human cancer cell lines HEP3BPN 11 (liver), MDA-MB 453 (breast), and HL 60 (leukemia) were assessed. Among all the compounds 8 L, 8q, 9n and 9p showed higher inhibitory activity on the viability of HL 60 than the standard methotrexate. These lead molecules were then tested for their potential to inhibit the activity of proangiogenic cytokines. The compound 9n showed significantly better inhibition against two cytokines viz. TNFα and Leptin as compared to the standard suramin, while 9p has activity comparable to suramin against IGF1, VEGF, FGFb, and Leptin. The 8q is found to be strong antiangiogenic agent against IGF1, VEGF and TGFβ; while 8 L has showed activity against TNFα, VEGF, and Leptin inhibition. Furthermore antioxidant potential of 8a–t and 9a-t compounds was screened using DPPH, OH and SOR radical scavenging activities. The OH radical scavenging activity of 8c and DPPH activities of 9n as well as 9o are significant as compared to respective standards ascorbic acid and α-tocopherol. The 8c, 9p and 9 h have also exhibited potential antioxidant activity. Additionally, we present in silico molecular docking data to provide the structural rationale of observed TNFα inhibition against newly synthesized compounds. Overall, the synthesized flutamide derivatives have not only anticancer activity, but also possess dual inhibitory effect (anti-angiogenesis and antioxidant) and hence can act as a promising avenue to develop further anticancer agents. |
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| Keywords: | Antiangiogenic Anticancer Antioxidant activity Flutamide Autodock |
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