Design, synthesis, in silico toxicity prediction, molecular docking, and evaluation of novel pyrazole derivatives as potential antiproliferative agents

Authors

  • Parameshwar Ravula Department of Pharmaceutical Chemistry, Guru Nanak Institutions Technical Campus, School of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad- 501301, India
  • Harinadha Babu Vamaraju Medicinal Chemistry Division, G. Pulla Reddy College of Pharmacy, Osmania University, Hyderabad - 500028, India
  • Manichandrika Paturi Department of Pharmaceutical Chemistry, Bojjam Narsimulu Pharmacy College for Woman, Jawaharlal Nehru Technological University, Hyderabad-500028, India
  • Narendra Sharath Chandra JN Department of Pharmaceutical Chemistry, Guru Nanak Institutions Technical Campus, School of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad- 501301, India
  • Swetha Kolli Medicinal Chemistry Division, G. Pulla Reddy College of Pharmacy, Osmania University, Hyderabad - 500028, India

DOI:

https://doi.org/10.17179/excli2016-103

Keywords:

pyrazolyl tetrazole acetic acids, antiproliferative activity, molecular modeling, VEGFR-2

Abstract

A new series of pyrazole derivatives were designed by docking into vascular endothelial growth factor receptor-2 (VEGFR-2) kinase active site. The designed compounds were synthesized and evaluated for in vitro antiproliferative activity against HT-29 colon and PC-3 prostate cancer cell lines, and angioinhibitory activity in chorioallantoic membrane (CAM) model. Based on the obtained antiproliferative activity results of in vitro and CAM assay, compounds 4b, 4c, 4f, 5b, 5c and 5f were selected, and tested for anticancer activity using in vivo ehrlich ascites carcinoma (EAC) bearing mice. Compound 5c showed the highest in vitro antiproliferative activity against HT-29 and PC-3 with IC50 values of 6.43 µM and 9.83 µM respectively and comparable to reference drug Doxorubicin. Results of in vivo anticancer activity revealed that compound 5c showed the highest percentage increase in life span ( %ILS), and mean survival time (MST) with 75.13 % and 32.4 ± 0.53 days respectively. Moreover, compound 5c demonstrated significant reduction of microvessel density (MVD) in CAM assay. In silico prediction of toxicities, and drug score profiles of designed compounds are promising. A correlation made between the results obtained by antiproliferative study and molecular docking studies suggest that the synthesized compounds may be beneficial as molecular scaffolds for antiproliferative activity.

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Published

2016-03-01

How to Cite

Ravula, P., Vamaraju, H. B., Paturi, M., Chandra JN, N. S., & Kolli, S. (2016). Design, synthesis, in silico toxicity prediction, molecular docking, and evaluation of novel pyrazole derivatives as potential antiproliferative agents. EXCLI Journal, 15, 187–202. https://doi.org/10.17179/excli2016-103

Issue

Vol. 15 (2016)

Section

Original articles

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