Anti-proliferative potential of triphenyl substituted pyrimidines against MDA-MB-231, HCT-116 and HT-29 cancer cell lines |
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| Institution: | 1. Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, Punjab 151001, India;2. Department of Microbiology, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab 151001, India;3. Laboratory of Organic and Medicinal Chemistry, Department of Chemistry, Central University of Punjab, Bathinda, Punjab 151001, India;1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500 037, Telangana, India;2. Division of Microbiology, CSIR-Central Drug Research Institute, Sitapur Road, Sector 10, Janakipuram Extension, Lucknow, 226031, Uttar Pradesh, India;1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;2. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;3. Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;1. Chemistry Department, Faculty of Science, Ain Shams University, Abbassia, Cairo 11566, Egypt;2. Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt;1. School of Basic Medical Science, Zhengzhou University, Zhengzhou 450001, China;2. School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China;3. Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;4. Department of Urology, University of California, Irvine, Orange, CA 92868, USA;1. Université de Limoges, Laboratoire PEIRENE EA 7500, Faculté de Pharmacie, 2 Rue Du Dr Marcland, 87025, Limoges Cedex, France;2. Université de Limoges, BISCEm NMR Platform, GEIST, 2 Rue Du Dr Marcland, 87025, Limoges Cedex, France;3. Université Grenoble Alpes, CEA, INSERM, IRIG, BGE U1038, Genetics & Chemogenomics, 17 Avenue des Martyrs, Grenoble, 38054, France |
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| Abstract: | A series of triphenyl substituted pyrimidines as analogous of colchicine and combretastatin A-4 was synthesized and evaluated for the antiproliferative potential. The compounds were screened against MDA-MB-231, HCT-116 and HT-29 cell lines using MTT assay. Most of the compounds displayed antiproliferative activity in low to sub micro molar concentration. Amongst the synthesized derivatives, compounds HK-2, HK-10 and HK-13 were found to be effective against all the three cancer cell lines. HK-2 exhibited IC50 values of 3.39 µM, 4.78 µM and 4.23 µM, HK-10 showed IC50 values of 0.81 µM, 5.89 µM, 4.96 µM and HK-13 showed IC50 values 3.24 µM, 4.93 µM and 4.73 µM against MDA-MB-231, HCT-116 and HT-29 cancer cell lines, respectively. HK-10 was found to be the most potent compound in the series with IC50 values of 0.81 µM against MDA-MB-231. In the cell cycle analysis, HK-2 and HK-10 showed cell arrest at G2/M phase of the cell cycle while HK-13 inhibited cell growth at the G1/G0 phase. All the three compounds showed cell death induced through apoptosis. In the docking studies, HK-2, HK-10 and HK-13 were found to fit well in the colchicine binding site of the tubulin. Some of the compounds in the current series were found to be promising against all the three cancer cell lines and may act as potent leads for further development. |
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| Keywords: | Antiproliferative agents Pyrimidines Colchicine binding site Tubulin polymerization inhibitors Combretastatin |
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