Synthesis of stable benzimidazole derivatives bearing pyrazole as anticancer and EGFR receptor inhibitors |
| |
| Affiliation: | 1. Department of Pharmaceutical Chemistry, School of Pharmaceutical Education & Research (Formerly Faculty of Pharmacy), Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India;2. Lab no 405, Institute of Genomics and Integrative Biology, New Delhi, India;3. Department of Pharmacology, School of Pharmaceutical Education & Research (Formerly Faculty of Pharmacy), Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India;1. School of Allied Health Sciences, De Montfort University, The Gateway, Leicester, LE1 9BH, UK;2. Department of Chemistry, Loughborough University, Loughborough, LE11 3TU, UK;3. Laboratory of Growth Regulators, Palacky University & Institute of Experimental Botany ASCR, Šlechtitelů 27, 783 71 Olomouc, Czech Republic;4. Advanced Light Source, Berkeley Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA;1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;2. Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Sakaka, Aljouf 2014, Saudi Arabia;3. Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates;4. Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;1. Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Cairo, 12622, Egypt;2. Department of Cancer Biology, National Cancer Institute, Cairo University, Egypt;3. Department of Pharmaceutical Sciences, Texas A&M University Irma Lerma Rangel College of Pharmacy Kingsville, TX 78363, United States;4. Department of Pharmaceutical Chemistry, College of Pharmacy, Helwan University, Cairo, Egypt;5. Department of Microbial Biotechnology, Division of Genetic Engineering & Biotechnology, National Research Centre, 12622, Cairo, Egypt;6. Department of Biochemistry, Division of Genetic Engineering and Biotechnology, National Research Centre, 12622, Cairo, Egypt;7. Pesticide Chemistry Department, National Research Centre, 12622, Cairo, Egypt;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. Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia;2. New Drug Discovery Research, Department of Medicinal Chemistry, Alwar Pharmacy College, Alwar 301030, Rajasthan, India;3. New Drug Discovery Research, Department of Medicinal Chemistry, Sunrise University, Alwar 301030, Rajasthan, India;4. School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia;5. Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, United States |
| |
| Abstract: | A new series of benzimidazole linked pyrazole derivatives were synthesized by cyclocondensation reaction through one-pot multicomponent reaction in absolute ethanol. All the synthesized compounds were tested for their in vitro anticancer activities on five human cancer cell lines including MCF-7, HaCaT, MDA-MB231, A549 and HepG2. EGFR receptor inhibitory activities were carried out for all the compounds. Majority of the compounds showed potent antiproliferative activity against the tested cancer cell lines. Compound 5a showed the most effective activity against the lungs cancer cell lines (IC50 = 2.2 µM) and EGFR binding (IC50 = 0.97 µM) affinity as compared to other members of the series. Compound 5a inhibited growth of A549 cancer cells by inducing a strong G2/M phase arrest. In addition, same compound inhibited growth of A549 cancer cells by inducing apoptosis. In molecular docking studies compound 5a was bound to the active pocket of the EGFR (PDB 1M17) with five key hydrogen bonds and two π-π interaction with binding energies ΔG = −34.581 Kcal/mol. |
| |
| Keywords: | Benzimidazole linked pyrazole Anticancer Apoptosis Docking studies Cardiomyopathy studies |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
