A Novel Bioinformatics Approach: to Design Novel 1, 4-Benzothiazine Derivatives for the Treatment of Hypertension

Amit Rai¹*, Vinit Raj¹, Deepak Kumar¹

1. Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University)Vidya Vihar, Raebreli Road, Lucknow-226025(U.P.), India.

ABSTRACT

Angiotensin I-converting enzyme (ACE) is a key therapeutic target for combating hypertension and related cardiovascular diseases. ACE inhibitory novel designed substituted 1, 4-benzothiazine derivatives offer the prospect of enhanced potency, high specificity, and no or low side effect. Novel 1,4-benzothiazine derivatives were designed keeping in view the structural requirement of pharmacophore and Quantitatively structure Activity Relationship (QSAR).In the docking study, the most active compounds of the series were, AR 1, AR 2 and AR 3 exhibited good binding properties. Result reveals that the protein-ligand interaction energy of derivatives AR 1, AR 2 and AR 3 were -7.51 kcal/mol, -8.80 kcal/mol and -7.63 kcal/mol, which is slightly greater than the marketed antihypertensive Losartan drug as -5.51 kcal/mol, so that the derivatives have satisfactory affinity with established hypertensive receptor namely Angiotensin converted enzyme II. A computational study was also carried out including prediction of pharmacokinetic properties, toxicity and bioactivity studies. The percentage of absorption (%ABS) was calculated and observed that all titled compounds exhibited a better %ABS %ABS ranging 90.54, 91.42 and 90.55 respectively and compared than standard Losartan drug as %ABS 77.06.Although other pharmacological parameters were better than the standard drug. The above observation suggested that these compounds would serve as better lead compound for antihypertensive screening for future drug design perspective.

Keywords: 1, 4-benzothiazine derivatives, Anti hypertension activity, Computational study and ACE-II.