Collect. Czech. Chem. Commun. 1997, 62, 1503-1510

Combination of the Topliss Approach with the Free-Wilson Analysis in the Study of Antimycobacterial Activityof 4-Alkylthiobenzanilides

Jiří Kuneša, Jiří Jáchyma, Petr Jiráskoa, Želmíra Odlerováb and Karel Waissera

a Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, 500 05 Hradec Králové, Czech Republic
b Institute of Preventive and Clinical Medicine, 833 01 Bratislava, Slovak Republic


On the basis of a preliminary study of the antimycobacterial activity of thiobenzanilides, a group of 4'-isopropyl- and 4'-butylthiobenzanilides have been synthesized and tested against Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium and Mycobacterium fortuitum. The effect of the substituents on minimum inhibitory concentrations was calculated by the Free-Wilson method. The separated values were analyzed by the Topliss approach. The substitution of the thiobenzanilide in position 4' by the isopropyl group or butyl group increased the antimycobacterial activity less than the cyclohexyl group. The substitution in position 4 decreased the activity by the steric effect.

Keywords: Thiobenzanilides; Tuberculostatics; Mycobacterium spp.; Structure–activity relationships; Free-Wilson analysis; Topliss approach.