Rationalization of physicochemical characters of oxazolyl thiosemicarbazone analogs towards multi-drug resistant tuberculosis: a QSAR approach.
The emergence of multi-drug resistant (MDR) strains of Mycobacterium tuberculosis and the continuing pandemic of tuberculosis emphasizes the urgent need for the development of new and potent anti-tubercular agents. In an effort to develop new and more effective agents to treat tuberculosis emphasis was focused on quantification of structure-activity relationship of oxazolyl thiosemicarbazone derivatives. The de novo analysis gave insight to some important structural features i.e. nitro group on phenyl ring at R(1) position is optimal for the activity and might be responsible for electronic interaction, while phenyl ring at R position interact with the hydrophobic pocket more effectively as compared to unsubstituted or methyl substituted analogs. Hansch approach offered the understanding and parameterization of interactions of the inhibitor with receptor. Similarly QSAR analysis gave some important physicochemical properties, i.e. empirical aromatic index (ARR) and 3D-MoRSE code value of scattering angle at 8A(-1). These two physicochemical properties shall be helpful in the development of more potent analogs.
Gupta
Revathi A
RA
Molecular Modelling Study Group, CADD Laboratory, Department of Pharmacy, Shri G.S. Institute of Technology and Science, 23 Park Road, Indore 452003, MP, India.
Gupta
Arun K
AK
Soni
Love K
LK
Kaskhedikar
S G
SG
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003625:Data Collection; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
D000995:Antitubercular Agents; D013882:Thiosemicarbazones