Studies on heterocyclic compounds: 1,3-thiazolidin-4-one derivatives. III. Biological activity of halogenated 2,3-diaryl-1,3-thiazolidin-4-ones.

In previous communications from these laboratories, thiazolidinone derivatives of general formula (A) were synthesized and screened for antimicrobial activity. (formula; see text) where: X = H, CH3 Ar = phenyl Ar' = fluorinated or chlorinated phenyl The present communication is in part concerned with further extension of these studies to variously halogenated thiazolidinones of general formula (B). (formula; see text) where: X = H, CH3 R = H, 2-F, 3-F, 4-F, 3-Cl, 4-Cl R' = H, 4-F, 4-Cl These compounds were prepared by the general synthetic procedure previously reported for the 1,3-thiazolidin-4-one derivatives already prepared and screened in this SARs program. The general synthetic approach involves the cyclocondensation of the appropriate Schiff bases with alpha-mercaptoalkanoic acids such as thioglycolic and thiolactic acid. The prepared compounds were tested for their possible activity by a disk-diffusion assay (Kirby-Bauer modified). The organisms used were: S. aureus, S. beta-haemoliticus, B. subtilis, M. paratuberculosis 607, S. typhi, Kl. pneumoniae, E. coli Bb, Ps. aeruginosa, C. albicans, A. niger, S. cerevisiae. The results of this antimicrobial screening showed that the prepared compounds exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi. The second half of this report deals with the structure-activity relationships in all the compounds prepared and studied in this research program. For comparison of antimicrobial activity, the growth inhibitory activity of all the halogenated thiazolidinones of type (A) and (B), prepared and screened in this SARs study, were tabulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Structure-activity relationships of hydrazono derivatives of biological interest.

The following hydrazono derivatives (I-XXIII) of type (A), (formula; see text) where: X = NO2 (II, IV, VI, VIII, X, XIV-XXIII), X = H (I, III, V, VII, IX, XI, XII, XIII), and Y = H (I, II); 3-Cl (III, IV); 4-Cl (V, VI); 3,4-Cl2 (VII, VIII); 2,6-Cl2 (IX, X); 2-NO2 (XI); 3-NO2 (XII); 4-NO2 (XIII, XIV); 2-F (XV); 3-F (XVI); 4-F (XVII); 2-OH (XVIII); 4-OH (XIX); 2,4-(OH)2(XX); 2,4,6-(OH)3(XXI); 2,3-(OH,NO2) (XXII); 2,4-(NO2)2 (XXIII), were prepared and tested for antibacterial and antifungal activity. All of these compounds were prepared in satisfactory yield by reaction of aromatic aldehydes with 2-furoyl and 5-nitro-2-furoyl hydrazide. The hydrazono derivatives I-XXIII prepared in this investigation were screened for antimicrobial activity by a disk-diffusion assay (Kirby-Bauer modified). The organisms used were laboratory cultures of S. aureus, S. -haemoliticus, B. subtilis, M. paratuberculosis, E. coli, S. typhi, Ps. aeruginosa, K1. pneumoniae, A. niger, S. cerevisiae, C. albicans. The results of this study showed that a number of the prepared hydrazono derivatives exhibited varying degrees of activity against Gram-positive and Gram-negative bacteria. Compounds IV and XV possessed broad spectrum "in vitro" against Gram-positive and Gram-negative bacteria. Compounds XII greater than IV greater than XV showed inhibitory activity especially toward S. aureus. Compounds IV greater than XV greater than XVI were especially active against E. coli. Compounds XV greater than IV were especially inhibitory toward S. typhi and most of the prepared compounds inhibited considerably Ps. aeruginosa and K1. pneumoniae.