Collect. Czech. Chem. Commun. 2003, 68, 1275-1294

On the Relationship between the Structure and Antimycobacterial Activity of Substituted N-Benzylsalicylamides

Karel Waissera,*, Milan Peřinaa, Věra Klimešováa and Jarmila Kaustováb

a Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Heyrovského 1203, CZ-500 05 Hradec Králové, Czech Republic
b National Reference Laboratory for Mycobacterium kansasii, Institute of Hygiene, Partyzánské nám. 7, CZ-728 92 Ostrava, Czech Republic


Sixty-six N-benzylsalicylamides substituted in the acyl moiety in positions 3, 4 or 5 and in position 4 on the benzylic aromatic ring were synthesized. The compounds were tested for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium. To evaluate structure-antimycobacterial activity relationships (QSARs), approaches based on the Free-Wilson as well as a combination of the Free-Wilson and Hansch methods were employed (substituent constants were used to describe the influence of the benzyl substituents, indicator parameters were used for the substituents on the acyl moiety). The use of the Hammett constants for benzyl substituents was not important for QSAR equations. The quadratic representation of lipophilicity parameters (π2) was significant only in QSAR equations of antimycobacterial activity against M. avium.

Keywords: Tuberculostatic; Antituberculotics; Salicylamides; QSAR; Substituent effects; Structure–activity relationships; Antimicrobial activity; Free-Wilson method.

References: 14 live references.