SYNTHESIS AND 2D-QSAR STUDY OF SOME NOVEL SUBSTITUTED BENZIMIDAZOLE DERIVATIVES AS ANTITUBERCULAR AGENTSAbstract
In the present work, a series of some novel substituted benzimidazole derivatives were efficiently synthesized, and a thin layer chromatography study confirmed the completion of the reaction on silica gel-G plates. The characterization was done through recording spectra of FTIR using Jasco FTIR-460 plus spectrophotometer, recording spectra of 1HNMR with the help of spectrometer, specifically BRUKER 400MHz. The synthesized substituted novel benzimidazole derivatives were screened for their in-vitro antitubercular activity by the Microplate Alamar Blue Assay (MABA) method against Mycobacterium tuberculosis (H37Rv strain) with their 2D-QSAR studies. The antitubercular activity results confirmed that compounds DPK3d1, DPK2d1, DPK2d2, DPK2d3, DPK4B1d2, DPK4B2d1, and DPK4B2d2 had shown potent antitubercular activity as compared to standard drugs. These synthesized derivatives were selected 2D-QSAR analysis with their different models such as multiple linear regression (MLR), and partial least squares regression (PLR) analysis were generated to find out the correlation between physicochemical properties parameters and their biological activity. 2D-QSAR models such as MLR and PLS method studies generated an equation showing that descriptors SsOHcount, Ipc Average, Delta AlphaA, Delta AlphaB, and chi6chain are directly proportional to the antitubercular activity. The prediction activity in the test set is rewarding for the development of antitubercular therapy.
D. P. Kardile * and M. K. Shirsat
Department of Pharmaceutical Sciences, Madhav University, Pindwara, Rajasthan, India.
03 April 2020
11 August 2020
10 September 2020
01 April 2021