Tuberculosis is an infection caused by Mycobacterium tuberculosis, which commonly affects the respiratory tract, i.e. lungs.1) It is termed as "a global health emergency" by world health organization (WHO) in 1993 as it affects 1.7 billion people per year, that is equal to one-third of the entire world population. The first line of drugs used in the treatment of tuberculosis (TB) is a combination of isoniazid, rifampicin, pyrazinamide and ethambutol. The high concentration of lipids in the cell wall of M. tuberculosis has been attributed to its resistant to antibiotics. The lipid fraction of cell wall consists of three major components mycolic acids, cord factor and wax-D. Isoniazid is known to inhibit the synthesis of mycolic acid. Ethambutol is known to inhibit the incorporation of mycolic acid into the cell wall. Rifampicin acts by binding to DNA-dependent RNA polymerase and inhibits initiation of RNA synthesis. Pyrazinoic acid, the active form of pyrazinamide, is reported by Zhang Y., et al. to inhibit M. tuberculosis membrane transport function and disrupt membrane energetics.2) It is expected that the disease can be completely eliminated with the help of combination therapy, but these hopes were dashed with the advent of drug resistant strains. The development of drug resistant strains is due to point mutations in the bacterial chromosome, resulting in changes in the antibiotic target that renders the strain no longer susceptible to the drug.Thus the increasing clinical importance of tuberculosis has lent additional urgency to researchers to identify new and effective antimycobacterial compounds. Literature survey reveals that chalcones, flavones and flavanones possess antiinflammatory, 3) anticancer, 4) antileishmanial, 5) antimalarial, 6) antimicrobial and antioxidant 7) activities. It is reported that the chalcones and their derivatives are more effective against Gram-positive bacteria than against Gram-negative bacteria. 8)But it is interesting to note that they are also effective against this acid-fast bacillus which is neither Gram-positive nor negative. These compounds show very good activity against H37Rv strain. Understanding the effect of structural features on the activity would help the researchers to design new molecules that may exhibit higher activity. Quantitative structure activity relationship (QSAR) approach is better for designing new drugs when the target is not known or if there are multiple targets.QSAR studies on heterocyclic analogues of salicylanilides performed through the combination of Free-Wilson and Hansch approach explains the influences of electronic and hydrophobic properties.9) Gupta M. K., et al. have observed that topological descriptors are correlated with the antimycobacterial activity of nitro/acetamido alkenol and chloro/amino alkenol derivatives.10) 3D-QSAR uses three-dimensional properties of the molecules (particularly steric and electrostatic factors) and correlates these descriptors with the biological activity. 3D-QSAR studies carried out by Shagufta, et al. o...

Quantitative structure activity relationships (QSAR) were developed relating the 14th and 21st day antituberculosis activity against H(37)Rv strain of Mycobacterium tuberculi and antibacterial activity against Staphylococcus aureus ATCC3750, Bacillus subtilis 6633, Escherichia coli ATCC3750, and Salmonella typhi NCTC786 of 55 pyrazine containing thiazolines and thiazolidinones, with the molecular descriptors. The developed models were able to fit the data well (r(2) = 0.69-0.87) and had reasonable predictive capability (q(2) > 0.62). The data were also divided into a training set and a test set, the former was used to develop the QSAR and the latter was used to evaluate the predictive capability of these developed models. In all the cases, the models were able to predict the test data set reasonably well. Predominantly, pyrazine ring is well-known for its antimycobacterial activity and hence these equation could be used to design newer analogues with higher activity. These compounds also possess both antitubercular and antibacterial activity. Descriptors pertaining to electronic, topology, and hydrophobicity of the molecules appear in the model equations.

Quantitative structure activity relationships were developed for seventeen propenone derivatives reported in the literature that act as dual COX and 5-LOX inhibitors. Predominantly spatial, thermodynamic, topological, and electronic descriptors appear in the models. Docking between these compounds and COX-1, COX-2 and 5-LOX enzymes was also performed and mathematical relationships were developed between the binding energy and activity.