title: Structure-activity relationship studies of microbiologically active thiosemicarbazides derived from hydroxybenzoic acid hydrazides.
abstract: Forty-five derivatives of thiosemicarbazide were synthesized, and their antibacterial activity against Gram-positive and Gram-negative bacteria was evaluated. Some of the described compounds exhibited interesting activity against reference strains of Gram-positive bacteria, whereas only two derivatives had the ability to inhibit the growth of Gram-negative species (Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, Proteus mirabilis ATCC 12453). The most potent antimicrobial activity was observed in the cases of salicylic acid hydrazide derivatives. The differences in activity inspired us to conduct conformational analysis using molecular mechanics level. The obtained results suggest that the molecule geometry, especially at the N4-terminus of thiosemicarbazide skeleton, determines the antibacterial activity. Unfortunately, in opposition to what we expected, only one of the tested compounds inhibited the activity of the topoIV enzyme, and none of them was active against DNA gyrase.
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Medical University, Chodzki 4A, Lublin, 20-093, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Plech
authors.forename: Agata
authors.initials: A
authors.lastname: Paneth
authors.forename: Barbara
authors.initials: B
authors.lastname: Kaproń
authors.forename: Urszula
authors.initials: U
authors.lastname: Kosikowska
authors.forename: Anna
authors.initials: A
authors.lastname: Malm
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Strzelczyk
authors.forename: Paweł
authors.initials: P
authors.lastname: Stączek
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D027081:DNA Gyrase / Q000737:chemistry / Q000378:metabolism; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006834:Hydrazines / Q000737:chemistry*; D062385:Hydroxybenzoates / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D012663:Semicarbazides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006834:Hydrazines; D062385:Hydroxybenzoates; D012663:Semicarbazides; C029424:hydrazine; C005151:thiosemicarbazide; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase
keywords: drug design; enzymatic mechanism; structure-activity relationships; thiosemicarbazide derivatives