DESIGN, SYNTHESIS AND IN VITRO ANTI-CANCER ACTIVITY OF NOVEL 1,2,4-TRIAZOLE DERIVATIVES

  • Stephen Philip JSS College of Pharmacy, JSS University Mysore India
  • Madhusudan N Purohit JSS College of Pharmacy, JSS University Mysore India
  • Krishna K L JSS College of Pharmacy, JSS University Mysore India
  • Eshwar M S JSS College of Pharmacy, JSS University Mysore India
  • Tanuj Raizaday JSS College of Pharmacy, JSS University Mysore India
  • Prudhvi S JSS College of Pharmacy, JSS University Mysore India
  • Gurubasavaraj V Pujar JSS College of Pharmacy, JSS University Mysore India

Abstract

Objective: DNA topoisomerase is one of the important targets for anticancer agents. Many triazole derivatives have been shown to possess cytotoxic activity. In this paper, we present the design and in silico docking of a virtual library of molecules with DNA topoisomerase II along with their synthesis and In vitro cytotoxicity profile.

Methods: Sybyl X 2.1 programmesss were used to perform the docking experiments on DNA topoisomerase II using etoposide as ligand. In vitro anticancer activity was carried out by trypan blue exclusion assay against EAC cells. DNA fragmentation studies were performed by Gel electrophoresis to identify the cause of cell death induced by these compounds.

Results: Among the compounds studied for docking, 12c generated the highest docking score (13.66) and showed hydrogen bonding interactions with glycine 778 at a distance of 1.879 A˚. the compounds 12c & 12g showed the highest level of cytotoxicity with IC50 value of 0.55 μM and 0.62 μM respectively. Compounds 12c and12g were subjected to DNA fragmentation studies to identify the cause of cell death induced by these compounds. Gel electrophoresis of these compounds showed a typical feature of apoptosis ladders in agarose gel. Compound 12c was able to induce apoptosis at a concentration of about 3 μM.

Conclusion: A series of bis-triazoles were synthesized targeted to DNA topoisomerase II and evaluated their In vitro cytotoxicity. The compound 12c was found to be most active and also exhibited apoptosis inducing potential.

 

Keywords: DNA Topoisomerase, Bis-triazole, Cytotoxicity, DNA fragmentation, Apoptosis.

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Author Biographies

Stephen Philip, JSS College of Pharmacy, JSS University Mysore India
Student
Madhusudan N Purohit, JSS College of Pharmacy, JSS University Mysore India
Professor of Pharmaceutical Chemistry
Krishna K L, JSS College of Pharmacy, JSS University Mysore India
Assistant Professor of Pharmacology
Eshwar M S, JSS College of Pharmacy, JSS University Mysore India
Student
Tanuj Raizaday, JSS College of Pharmacy, JSS University Mysore India
Student
Prudhvi S, JSS College of Pharmacy, JSS University Mysore India
Student
Gurubasavaraj V Pujar, JSS College of Pharmacy, JSS University Mysore India
Professor and Head dept of Pharmaceutical chemistry

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How to Cite
Philip, S., M. N. Purohit, K. K. L, E. M. S, T. Raizaday, P. S, and G. V. Pujar. “DESIGN, SYNTHESIS AND IN VITRO ANTI-CANCER ACTIVITY OF NOVEL 1,2,4-TRIAZOLE DERIVATIVES”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 6, no. 10, 1, pp. 185-9, https://innovareacademics.in/journals/index.php/ijpps/article/view/1656.
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