Design of compounds having good anti-tubercular activity is gaining much importance in the field of tuberculosis research due to reemergence of antibiotic resistance strains. In this paper quantitative structure activity relationships (QSAR) were developed on chalcones, chalcone-like compounds, flavones and flavanones to understand the relationship between biological activity and structural features. Genetic function approximation (GFA) method was used to identify the descriptors that would lead to good regression equations. The best molecular descriptors identified were Jurs descriptors (Jurs charged partial surface area), hydrogen bond donor, principal moment of inertia, molecular energy, dipole magnetic, molecular area, absorption, distribution, metabolism and excretion (ADME) properties and Chi indices (Kier & Hall chi connectivity indices). Excellent statistically significant models were developed by this approach (r2=0.8—0.97) for the four groups of compounds. The cross validated r2 (XV r2) which is an indication of the predictive capability of the model for all the cases was also very good (=0.79—0.94).

Novel sixteen chalcones and thirteen 1,3,5‐triphenyl‐2‐pyrazolines were synthesized and characterized using FT‐IR, HR‐Mass, NMR (¹H‐NMR, ¹³C‐NMR, 135 DEPT, ¹H–¹H CoSY and ¹H and ¹³C CoSY) and XRD. These compounds were evaluated for their antibacterial activity against six micro‐organisms, namely Bacillus subtilis NCIM 2718, Staphylococcus aureus NCIM 5021, Salmonella typhi NCIM 2501, Enterobacter aerogenes NCIM 5139, Pseudomonas aeruginosa NCIM 5029, and Proteus vulgaris NCIM 2813 by twofold dilution method using resazurin as the indicator dye. In the case of chalcones, compounds with hydroxyl and bromo substitutions in the B‐ring favor activity and benzyloxy substitution irrespective of its position in the A‐ring. In the case of 1,3,5‐triphenyl‐2‐pyrazolines, chloro substitution in the A‐ring favors activity. Hydrophilic/lipophilic balance of the compounds plays a major role in their antibacterial activity.