title: Synthesis of novel sulfonamide-1,2,4-triazoles, 1,3,4-thiadiazoles and 1,3,4-oxadiazoles, as potential antibacterial and antifungal agents. Biological evaluation and conformational analysis studies.
abstract: The significant antifungal activity of a series of sulfonamide-1,2,4-triazole and 1,3,4-thiazole derivatives against a series of micromycetes, compared to the commercial fungicide bifonazole has been reported. These compounds have also shown a comparable bactericidal effect to that of streptomycin and better activity than chloramphenicol against various bacteria. In view of the potential biological activity of members of the 1,2,4-triazole, 1,3,4-thiadiazole and 1,3,4-oxadiazole ring systems and in continuation of our search for bioactive molecules, we designed the synthesis of a series of novel sulfonamide-1,2,4-triazoles, -1,3,4-thiadiazoles and -1,3,4-oxadiazoles emphasizing, in particular, on the strategy of combining two chemically different but pharmacologically compatible molecules (the sulfomamide nucleus and the five member) heterocycles in one frame. Synthesized compounds were tested in vitro for antibacterial and antifungal activity and some analogues exhibited very promising results especially as antifungal agents. In order to explain structure-activity relationships, conformational analysis was performed for active and less active analogues using NMR spectroscopy and molecular modeling techniques. Furthermore, molecular properties which can be further used as descriptors for SAR studies, were predicted for the synthesized analogues. In general, antifungal activity seems to depend more on the triazol-3-thione moiety rather than the different length of the alkyl chain substitutions.
authors.affiliation: Laboratory of Molecular Analysis, Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vas. Constantinou Ave., 11635 Athens, Greece. pzoump@eie.gr
authors.forename: P
authors.initials: P
authors.lastname: Zoumpoulakis
authors.forename: Ch
authors.initials: Ch
authors.lastname: Camoutsis
authors.forename: G
authors.initials: G
authors.lastname: Pairas
authors.forename: M
authors.initials: M
authors.lastname: Soković
authors.forename: J
authors.initials: J
authors.lastname: Glamočlija
authors.forename: C
authors.initials: C
authors.lastname: Potamitis
authors.forename: A
authors.initials: A
authors.lastname: Pitsas
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D005658:Fungi / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D010069:Oxadiazoles; D013830:Thiadiazoles; D014230:Triazoles; C058949:1,3,4-thiadiazole; C045575:1,2,4-triazole