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

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

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 <b>5a</b>–<b>r</b> were designed and synthesized via the click reaction. Th...

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Main 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
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Molecules
Subjects:
drug design
1,2,3-triazole-uracil
VEGFR-2
in silico docking
MTT assay
anti-cancer agents
Online Access:https://www.mdpi.com/1420-3049/26/7/1952
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spelling doaj-f2a1fc8377bf4c8f99c7d98ae512a0f52021-03-30T23:06:03ZengMDPI AGMolecules1420-30492021-03-01261952195210.3390/molecules26071952Synthesis and Rational Design of New Appended 1,2,3-Triazole-Uracil Ensembles as Promising Anti-Tumor Agents via In Silico VEGFR-2 Transferase InhibitionNadipolla Naresh Reddy0Sung-Jen Hung1Merugu Kumara Swamy2Ananthula Sanjeev3Vankadari Srinivasa Rao4Rondla Rohini5Atcha Krishnam Raju6Kuthati Bhaskar7Anren Hu8Puchakayala Muralidhar Reddy9Department of Chemistry, Osmania University, Hyderabad, Telangana 500007, IndiaDepartment of Dermatology, Buddhist Tzu-Chi General Hospital, Hualien 97002, TaiwanDepartment of Chemistry, Osmania University, Hyderabad, Telangana 500007, IndiaDepartment of Chemistry, Osmania University, Hyderabad, Telangana 500007, IndiaDepartment of Chemistry, Osmania University, Hyderabad, Telangana 500007, IndiaDepartment of Chemistry, Osmania University, Hyderabad, Telangana 500007, IndiaDepartment of Chemistry, Nizam College, Osmania University, Hyderabad 500001, IndiaDepartment of Chemistry, Osmania University, Hyderabad, Telangana 500007, IndiaInstitute of Medical Sciences, Tzu-Chi University, Hualien 97002, TaiwanDepartment of Chemistry, Osmania University, Hyderabad, Telangana 500007, IndiaAngiogenesis 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 <b>5a</b>–<b>r</b> were designed and synthesized via the click reaction. The ligands were well characterized using <sup>1</sup>H-, <sup>13</sup>C-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 <b>5h</b> showed higher growth inhibition activity than the positive control, 5-fluorouracil (5-FU), against both HeLa and HUH-7 cells with IC<sub>50</sub> values of 4.5 and 7.7 μM respectively. Interestingly, the compounds <b>5a</b>–<b>r</b> 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.https://www.mdpi.com/1420-3049/26/7/1952drug design1,2,3-triazole-uracilVEGFR-2in silico dockingMTT assayanti-cancer agents
collection DOAJ
language English
format Article
sources DOAJ
author 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
spellingShingle 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
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
Molecules
drug design
1,2,3-triazole-uracil
VEGFR-2
in silico docking
MTT assay
anti-cancer agents
author_facet 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
author_sort Nadipolla Naresh Reddy
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2021-03-01
description 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 <b>5a</b>–<b>r</b> were designed and synthesized via the click reaction. The ligands were well characterized using <sup>1</sup>H-, <sup>13</sup>C-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 <b>5h</b> showed higher growth inhibition activity than the positive control, 5-fluorouracil (5-FU), against both HeLa and HUH-7 cells with IC<sub>50</sub> values of 4.5 and 7.7 μM respectively. Interestingly, the compounds <b>5a</b>–<b>r</b> 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.
topic drug design
1,2,3-triazole-uracil
VEGFR-2
in silico docking
MTT assay
anti-cancer agents
url https://www.mdpi.com/1420-3049/26/7/1952
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