QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP STUDIES OF SULFADIAZINE- SALICYLALDEHYDE SCHIFF BASE AS AN ANTI-MYCOBACTERIAL AGENTSAbstract
Quantitative structure activity relationship is among the most widely used computational technology for analogue-based drug design. A molecular modelling approach using sulfadiazine- salicylaldehyde Schiff base analogue as anti-mycobacterial activity from recently reported literature were taken and was designed using MOE 2009.10. Sulfanilamide sulfa drugs have been shown to inhibit dihydropteroate synthetase. In order to develop a pharmacophoric model for this inhibition, quantitative structure-activity relationship (QSAR) for sulfa drugs active against DHPS have been studied. Multiple linear regression analysis was performed to derive quantitative structure activity relationship models which were further evaluated internally as well as externally for the prediction of activity. Accurate minimum inhibitory concentrations (µM) were collected for 19 analogs, and other parameters, such as partition coefficients, molar refractivity, dipole moment, electrostatic interactions, lowest unoccupied molecular orbital (LUMO), highest unoccupied molecular orbital (HOMO), topological polar surface area were calculated. A data set of 19 analogs, all having a common sulphadiazine moiety, provided a cross-validated correlation coefficient (r2) value of 0.5998 and root mean square error value of 0.3829. The resulting QSAR pharmacophore model generated from the present study should be useful in the design of a similar group of more potent substituted compounds of Schiff base of sulpha drugs analogues as anti-mycobacterial agents.
P. Thangavelu *, M. Ramakrishnan, K. Mani, K. Somasundram, D. Srinivas and S. Thangavel
Nandha College of Pharmacy, Koorapalayam Pirivu, Pitchandam Palayam Post, Erode, Tamil Nadu, India.
13 April, 2018
13 June, 2018
26 June, 2018
01 December, 2018