No abstract

A number of solute descriptors that relate to the ability of a solute to take part in solutesolvent interactions have been identiüed, quantiüed and incorporated into a multiple linear regression equation. This general solvation equation can then be used for the correlation and prediction of solute eþ ects in transport processes, that is, processes in which the main step is either the equilibrium transfer, or the rate of transfer, of a solute from one phase to another. Examples discussed include the solubility of gases and vapours in water, various water-solvent partitions, blood-brain distribution, brain perfusion, and skin permeability.

Azetidin-2-one analogues are reported to exhibit various pharmacological activities like cholesterol absorption inhibitory activity, human tryptase, thrombin and chymase inhibitory activity, vasopressin V1a antagonist activity, antidiabetic, anti-inflammatory, antiparkinsonian and anti-HIV activity in addition to antimicrobial. 1-6 In the present study, Isoniazid (INH), the established antitubercular drug was selected as the lead for the design and development of antitubercular agents with minimal toxic effects. A novel series of amino azetidinones were designed from corresponding azetidin-2-ones using various in silico methods. Docking studies were performed at Mtb enoyl acp reductase (4DRE) and the derivatives exhibited best docking scores were prepared from corresponding azetidin-2-ones by treating with various molecules containing amino groups in the presence of TEA. Azetidin-2-ones in turn were obtained from a series of INH Schiff bases by reaction with chloro acetyl chloride. Structures of the newly synthesized compounds were assigned on the basis of elemental analysis, IR, 1 H NMR, 13 CNMR and mass spectral studies. The newly synthesized compounds were screened for their in vitro antitubercular activity using Alamar blue assay method and the hepatotoxicity was determined by MTT assay method using chang liver cells. AAZ1V, the amino azetidinone obtained from N-[3-chloro-2-(4-chlorophenyl)-4-oxoazetidin-1-yl] pyridine-4-carboxamide (AZ1V) by combining with 4-amino 1, 2, 4-triazole produced significant antitubercular activity. The percentage viability produced by AAZ1V against Chang liver cells for hepatotoxicity was better than the percentage viability produced by INH.

Several algorithms that use hydrogen bond descriptors have been published for the permeation of compounds from aqueous solution through human stratum corneum. In the present work, all the skin permeability coefficients, Kp in cm s-1, used in these algorithms for non-steroids have been correlated through the Abraham equation to give a new algorithm: [equation: see text] where n is the number of solutes, r is the correlation coefficient, s.d. is the standard deviation, and F is the F-statistic. The solute descriptors are: R2 an excess molar refraction, pi 2H the dipolarity/polarizability, sigma alpha 2H and sigma beta 2H the overall or effective hydrogen-bond acidity and basicity, and Vx the McGowan characteristic volume. Equation 1 is a reasonably good predictor of log Kp values for steroids as given by Johnson et al, but not for those given by Scheuplein.