Design synthesis biological and toxicological evaluation of novel indole derivatives

Abstract

In the cancer therapy, some drug combinations are administered following already newlineestablished procedures which have been carefully investigated in the clinical trials. The newlinemore compound drug regimen is the greater the risk of experiencing drug associated newlineproblems such as antagonistic events, medication errors, drug interactions, and noncompliance. newlineThe utilization of anticancer agents sometimes results in the use of other newlinemedicinal agents to cut down or prophylaxis from side-effects of the anticancer therapy, newlinethereby increasing the interaction potential of drugs. Furthermore, the disease of cancer newlineitself increases the requirement for more medicines. Cytotoxic drugs have a narrow newlinetherapeutic window and a complex medical profile. In cancer patients, pharmacokinetics newlinecan be altered because of the disease itself or by malnutrition, decreased levels of serumbinding newlineproteins, oedema, or liver and/or kidney dysfunction. Patients with cancer disease newlineare, therefore, at higher risk for drug interactions (DRP). Hence, it must be the target of all newlinehealth care providers to reduce treatment-associated risks to a minimum level in these newlinepatients. In the present research various indole analogues were designed with the help of newlineChemsketch followed by 3-dimensional optimization. Studies of molecular docking were newlinecarried out using Autodock and SWISSDOCK softwares to observe the binding newlineconnections with tubulin protein which is based on the crystalline structure (PDB ID: newline1SA0). Inferences of molecular docking of all software designed indole analogues were newlinematched on the basis of their minimum binding energy with a well known tubulin inhibitor newlinei.e. colchicine. Results were utilized to find out active compounds and series of such active newlinecompounds (4a1-4d11) was synthesized. FTIR, Proton NMR, Carbon-13 NMR, Mass newlinespectrophotometry and elemental analysis was used to characterize all compounds. All the newlineselected derivatives undergone in-vitro