IN-SILICO CHARACTERISATION, MOLECULAR DOCKING AND INVITRO EVALUATION OF TRIAZOLE DERIVATIVES AS POTENTIAL ANTI-CANCER AGENTS
Background: Cancer is defined as the uncontrolled growth and spread of abnormal cells. Mercaptopurine is used to treat many cancers such as-pancreatic, breast, colon, head& neck etc. Structure based and target based drug innovation are two main approaches in the new molecule development process. In structure based discovery, if the identified compound shows any significant pharmacological activity, then it is subjected to further development process and studies. Triazoles are heterocyclic five membered ring structures with 3 nitrogens and 2 carbon atoms. Triazoles are having wide spectrum of therapeutic activities such as anti-microbial, anti convulsant etc. The aim of the present study is to analyse the targeting efficiency of the drug through molecular docking, and synthesise and to perform In-Vitro anti-cancer studies for the justification of the docking results.
Objective: To perform in sillico molecular docking and in-vitro anticancer studies of proposed 1,2,4-triazole derivatives for the determination of their anti cancer activity.
Methodology: A series of ten triazole compounds with different substituents were drawn in ACD Lab Chem. Sketch software. Molecular and Biological properties were identified using Molinspiration software. The compounds that obeyed Lipinski rule of five are subjected for pharmacokinetic parameters prediction and docking analysis. Swiss dock ADME software is used for the prediction of Absorption, Distribution, Metabolism, Elimination. Then the compounds are docked with target enzymes in Chimera software1.14 version. The molecular docking studies revealed favorable molecular interactions and binding energies. The compounds that showed good docking results were synthesized through wet lab synthesis and further preceded for in vitro anti-cancer studies.
Results: Three compounds are selected for wet lab synthesis due to their good docking results compared to other compounds. The synthesized compounds are subjected to different In-vitro anticancer studies and found to be having potential anti-cancer activity.
Conclusion: The pharmacokinetic and docking studies conclude that the triazole compounds have potential as anti-cancer agents. The In-vitro anticancer studies revealed that the triazole derivatives are having high potency of anticancer activity against pancreatic cell lines.
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