Abstract

SYNTHESIS AND CONFORMATIONAL STUDIES OF N’-(3Z)-5- FLUORO-2-OXO-2,3-DIHYDRO-1H-INDOL-3-YLIDENE]-3- CARBOHYDRAZIDE WITH SPECIFIC PHARMACOPHORIC FEATURES.

Shazia Haider, Zafar Saied Saify, Afshan Naz, Kaniz Fizza, Tabinda Z. M, A.Arain, Toqeer ahmed Rao, *Seema Ashraf, Dr. Abdul Ghaffar

Abstract

Isonicotinic acid hydrazide (isoniazid,INH) and isatin are potential bioactive agents[1-5].Tuberculosis (TB) remains a major cause of mortality throughout the world. Resistance of Mycobacterium tuberculosis to antituberculosis drugs becomes very serious problem[6] Isonicotinic acid hydrazide (isoniazid, INH) belongs to the group of the first line antituberculosis drugs being in clinical practice over 50 years. Chemical modifications of isonicotinic acid hydrazide were performed on all parts of the molecule, but the activity of these derivatives against M. tuberculosis has not yet exceeded that of INH[7]. To overcome the resistance, combination of INH molecule with other active molecules is frequently applied[8]. This work was aimed at enhancing the antimycobacterial activity of INH by conjugation with keto group of 5 fluoro isatin and evaluate synergetic effect by conformational analysis using Argus lab, Ligand Scout and Marvin Sketch. The present work describes synthesis and the computer aided conformational analysis that is based on geometry optimization (active conformation) of drug by ArgusLab software. Argus Lab is the electronic structure program that is based on the quantum mechanics, it predicts the potential energies, molecular structures; geometry optimization of structure, vibration frequencies of coordinates of atoms, bond length, bond angle and reactions pathway [9] Conformational analysis of molecule is based on molecular mechanics, it is method for the calculation of molecular structures, conformational energies and other molecular properties using concept from classical mechanics. A molecule is considered as a collection of atoms held together by classical forces. These forces are described by potential energy function of structural features like bond lengths, bond angles and torsion angles etc. The energy (E) of the molecule is calculated as a sum of terms as in equation (1).

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