Synthesis and biological activities of new substituted thiazoline-quinoline derivatives

• Published in: Acta pharmaceutica (Zagreb, Croatia) Croatia), 2009-12, Vol.59 (4), p.365-382
• Main Authors: Hussein, Mostafa, Kafafy, Abdel-Hamid, Abdel-Moty, Samia, Abou-Ghadir, Ola
• Format: Article
• Language: English
• Subjects: Acetophenones - chemistry; Animals; Anti-Bacterial Agents - pharmacology; anti-inflammatory; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antifungal Agents - pharmacology; antimicrobial; antimikrobno djelovanje; Edema - chemically induced; fenacil bromid; Fluoroquinolones - pharmacology; Fungi - drug effects; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Indomethacin - pharmacology; Ketoconazole - pharmacology; kinolin; Lethal Dose 50; Male; Mice; phenacyl bromide; protuupalno djelovanje; quinoline; Quinolines - chemical synthesis; Quinolines - pharmacology; Rats; Stomach Ulcer - chemically induced; Thiazoles - chemical synthesis; Thiazoles - pharmacology; thiazoline; thiosemicarbazone; tiazolin; tiosemikarbazon; Toxicity Tests, Acute
• ISSN: 1330-0075; 1846-9558
• DOI: 10.2478/v10007-009-0033-8

5-Acyl-8-hydroxyquinoline-2-(3'-substituted-4'-aryl-2,3-dihydrothiazol-2'-ylidene)hydrazones, 5a-e to 10a-c, were prepared by the reaction of appropriate 5-acyl-8-hydroxyquinoline-4-substituted thiosemicarbazones 3a-e and phenacyl bromides 4a-e. Structures of the new compounds were verified on the basis of spectral and elemental analyses. Twenty-eight new compounds were tested for their possible antimicrobial activities. Most of the tested compounds showed weak to moderate antibacterial activity against most of the bacterial strains used in comparison with gatifloxacin as a reference drug. The test compounds showed weak to moderate antifungal activity against tested fungi in comparison with ketoconazole as a reference drug. On the other hand, the newly synthesized compounds were tested for their anti-inflammatory effects and most of them showed good to excellent anti-inflammatory activity compared to indomethacin. Moreover, ulcerogenicity and the median lethal dose (LD50) of the most active anti-inflammatory compounds 6b and 9e were determined in mice; they were non-toxic at doses up to 400 mg kg-1 after i.p. administration. 5-Acil-8-hidroksikinolin-2-(3'-supstituirani-4'-aril-2,3-dihidrotiazol-2'-iliden) hidrazoni 5a-e do 10a-c pripravljeni su reakcijom odgovarajućih 5-acil-8-hidroksikinolin-4-supstituiranih tiosemikarbazona 3a-e i fenacil bromida 4a-e. Strukture novih spojeva potvrđene su na temelju spektralnih i elementarnih analiza. Dvadeset osam novih spojeva testirano je na potencijalno antimikrobno djelovanje. Većina spojeva pokazuje slabo do umjereno antibakterijsko djelovanje protiv većine testiranih bakterijskih sojeva u usporedbi s gatifloksacinom kao referentim lijekom, te slabo do umjereno antifungalno djelovanje protiv gljivica u usporedbi s ketokonazolom kao referentnim lijekom. Testovi na protuupalno djelovanje pokazuju da većina spojeva posjeduje dobro ili snažno protuupalno djelovanje u usporedbi s indometacinom. Ulcerogeno djelovanje i srednje letalne doze (LD50) najaktivnijih spojeva 6b i 9e određene su na miševima. Rezultati pokazuju da su netoksični u dozama do 400 mg kg-1 nakon i.p. primjene.