Systematic Evaluation of Lipophilicity in Correlation with Pharmacophore Identification to Develop Potent Bacterial Inhibitors

Abstract

The widespread drug resistances against bacteria have been increased at an alarming rate and coerce to develop new designs with improved potency. Pharmacophore is the part of a molecular structure that responsible for a particular biological or pharmacological interaction. Lipophilicity is one of the key factors that play a crucial role in designing novel antibacterial agents. This parameter has been used in connection with blood–brain barrier (BBB) distribution or intestinal drug absorption and is sculpting by partition of a solute between n-octanol and water (LogP). It has been shown that increased lipophilicity can be correlated with increased biological activity, poorer aqueous solubility, more rapid metabolism and elimination, increased rate of skin penetration, increased plasma protein binding and faster action. Therefore, the purpose of this study is to estimate Lipophilicity in correlation with pharmacophoric nature of the compounds. In this study, a series of pyrazole derivatives were prepared through Schiff base condensation. Different groups were tuned as toxicophore at one end of molecular framework in order to identify their pharmacophoric function. All molecules were characterized through spectroscopic methods viz. IR, ESI–MS, 1H-NMR, 13C-NMR and elemental analysis. Antibacterial activities of all the derivatives were evaluated against Escherichia coli and Mycobacterium tuberculosis in comparison to standard drugs. The compound 4-bromo-N-((5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-yl)methylene)benzenamine (2j) was found the most promising among others with cytotoxicity 33.5 µg/mL determine through Brine Shrimp lethality bioassay. Electron withdrawing groups play a significant role in lipophilic control and inhibition action.