Synthesis and Rational Design of New Appended 1,2,3-Triazole-uracil Ensembles as Promising Anti-Tumor Agents via In Silico VEGFR-2 Transferase Inhibition |
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Authors: | Nadipolla Naresh Reddy Sung-Jen Hung Merugu Kumara Swamy Ananthula Sanjeev Vankadari Srinivasa Rao Rondla Rohini Atcha Krishnam Raju Kuthati Bhaskar Anren Hu Puchakayala Muralidhar Reddy |
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Institution: | 1.Department of Chemistry, Osmania University, Hyderabad, Telangana 500007, India; (N.N.R.); (M.K.S.); (A.S.); (V.S.R.); (R.R.); (K.B.);2.Department of Dermatology, Buddhist Tzu-Chi General Hospital, Hualien 97002, Taiwan;3.Institute of Medical Sciences, Tzu-Chi University, Hualien 97002, Taiwan;4.Department of Chemistry, Nizam College, Osmania University, Hyderabad 500001, India;5.Department of Laboratory Medicine and Biotechnology, College of Medicine, Tzu-Chi University, Hualien 97004, Taiwan |
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Abstract: | Angiogenesis inhibition is a key step towards the designing of new chemotherapeutic agents. In a view to preparing new molecular entities for cancer treatment, eighteen 1,2,3-triazole-uracil ensembles 5a–r were designed and synthesized via the click reaction. The ligands were well characterized using 1H-, 13C-NMR, elemental analysis and ESI-mass spectrometry. The in silico binding propinquities of the ligands were studied sequentially in the active region of VEGFR-2 using the Molegro virtual docker. All the compounds produced remarkable interactions and potentially inhibitory ligands against VEGFR-2 were obtained with high negative binding energies. Drug-likeness was assessed from the ADME properties. Cytotoxicity of the test compounds was measured against HeLa and HUH-7 tumor cells and NIH/3T3 normal cells by MTT assay. Compound 5h showed higher growth inhibition activity than the positive control, 5-fluorouracil (5-FU), against both HeLa and HUH-7 cells with IC50 values of 4.5 and 7.7 μM respectively. Interestingly, the compounds 5a–r did not show any cytotoxicity towards the normal cell lines. The results advance the position of substituted triazoles in the area of drug design with no ambiguity. |
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Keywords: | drug design 1 2 3-triazole-uracil VEGFR-2 in silico docking MTT assay anti-cancer agents |
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