New amide linked dimeric 1,2,3-triazoles bearing aryloxy scaffolds as a potent antiproliferative agents and EGFR tyrosine kinase phosphorylation inhibitors |
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| Institution: | 1. Department of Chemistry, Dr. Babasaheb Ambedkar, Marathwada University, Aurangabad 431 004, Maharashtra, India;2. Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, Maharashtra, India;3. Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education & Research, Shirpur 425 405, Maharashtra, India;4. Department of Pharmaceutical Chemistry, Durgamata Institute of Pharmacy, Dharmapuri, Parbhani 431 401, Maharashtra, India;5. Department of Animal Biology, University of Hyderabad, Hyderabad 500 046, India;1. Student Research Committe, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;2. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;3. Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;4. Student Research Committee, Ramsar International Branch, Mazandaran University of Medical Sciences, Iran;1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Culture West Road, Jinan 250012, PR China;2. Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;1. Department of Organic Synthesis & Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India;2. Academy of Scientific and Innovative Research (AcSIR), CSIR-Human Resource Development Centre (CSIR-HRDC) Campus, Ghaziabad, Uttar Pradesh 201002, India;3. Applied Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India;4. Laboratory of X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India;1. Instituto de Química Rosario, UNR, CONICET, Suipacha 531, S2002LRK, Rosario, Argentina;2. Cátedra de Microbiología, Virología y Parasitología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, S2002KTR, Rosario, Argentina;3. Institute of Chemical Biology & Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA;4. Consejo de Investigaciones, Universidad Nacional de Rosario, Argentina;5. Laboratorio de Microbiología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, S2002KTR, Rosario, Argentina;6. Departamento de Química Orgánica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario, Argentina;1. Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India;2. Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India;3. Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India;4. Department of Biotechnology, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India;5. Department of Pharmacognosy College of Pharmacy, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia;6. Pharmacognosy Group, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, 751 23, Uppsala, Sweden;1. Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt;2. Pharmaceutical Chemistry Department, College of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia;3. Sharjah Institute for Medical Research, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates;4. Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt;5. Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Aljouf, Sakaka, 2014, Saudi Arabia |
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| Abstract: | A search for potent antiproliferative agents has prompted to design and synthesize aryloxy bridged and amide linked dimeric 1,2,3-triazoles (7a–j) by using 1,3-dipolar cycloaddition reaction between 2-azido-N-phenylacetamides (4a–e) and bis(prop-2-yn-1-yloxy)benzenes (6a–b) via copper (I)-catalyzed click chemistry approach with good to excellent yields. All the newly synthesized compounds have been screened for their in vitro antiproliferative activities against two human cancer cell lines. The compounds 7d, 7e, 7h, 7i and 7j have revealed promising antiproliferative activity against human breast cancer cell line (MCF-7), whereas, the compounds 7a, 7b, 7c, 7i and 7j were observed as potent antiproliferative agents against human lung cancer cell line (A-549). The active compounds against MCF-7 have been also analysed for their mechanism of action by the enzymatic study, which shows that the compounds 7d, 7h and 7j were acts as active EGFR tyrosine kinase phosphorylation inhibitors. In support to this biological study, the molecular docking as well as in silico ADME properties of all the newly synthesized hybrids were predicted. |
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| Keywords: | Antiproliferative activity Click reaction Dimeric 1 2 3-triazoles EGFR tyrosine kinase phosphorylation inhibition Molecular docking study |
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