Prediction of new chromene-based inhibitors of tubulin using structure-based virtual screening and molecular dynamics simulation methods |
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| Affiliation: | 1. Department of Biology, Faculty of Science, Golestan University, Gorgan, Iran;2. Young Researchers and Elite Club, Bushehr Branch, Islamic Azad University, Bushehr, Iran;3. Persian Gulf Marine Biotechnology Research Center, Bushehr University of Medical Sciences, Bushehr, Iran;1. College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea;2. College of Pharmacy, CHA University, Pocheon 487-010, Republic of Korea;1. Department of Chemistry, Guru Nanak Dev University, Amritsar 143 005, India;2. Department of Microbiology, Guru Nanak Dev University, Amritsar 143 005, India;3. Department of Chemistry, Keene State College, Keene, NH 03435, USA;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bezmialem Vakif University, Fatih, Istanbul 34093, Turkey;2. Department of Biotechnology, Institute of Health Sciences, Bezmialem Vakif University, Fatih, Istanbul 34093, Turkey;1. Department of Chemistry, Faculty of Science, Selcuk University, Turkey;2. Department of Molecular Biology and Genetics, Faculty of Science, Necmettin Erbakan University, Turkey;3. Department of Biology, Faculty of Science, Selcuk University, Turkey;1. Department of Chemistry, G. S. Science, Arts and Commerce College, Khamgaon 444303, India;2. Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences and JB Tropical Disease Research Centre, Sevagram, Wardha 442102, India;1. College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450052, China;2. School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China |
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| Abstract: | Multidrug resistance (MDR) is one of the serious problems in cancer research that causes failure in chemotherapy. Chromene-based compounds have been proven to be the novel anti-MDR agents for inhibiting proliferation of tumor cells through tubulin polymerization inhibition of by binding at the colchicine binding site. In this study, we screened a chromene-based database of small molecules using physicochemical, ADMET properties and molecular docking to identify potential hit compounds. In order to validate our hit compounds, molecular dynamics simulations and related analysis were carried out and the results suggest that our hit compounds (PubChem CIDs: 16814409, 17594471, 57367244 and 69899719) can prove to be potential inhibitors of tubulin. The in silico results show that the present hits, like colchicine, effectively suppressed the dynamic instability of microtubules and induced microtubule-depolymerization and cell cycle arrest. |
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| Keywords: | Chromene Microtubule Tubulin Cancer Docking Molecular dynamics simulation Virtual screening |
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