Synthesis and Antimicrobial Activity of 5-(morpholinosulfonyl)isatin Derivatives Incorporating a Thiazole Moiety

Abstract

This article describes the synthesis of novel 5-(morpholinosulfonyl)isatin derivatives having biologically active thiazole moiety were synthesized via 2 synthetic routes. The first route involved interaction of 5-(morpholino-sulfonyl) isatin with aminothiazole derivatives to give the Schiff’s base derivatives (2, 3). The second route involved preparation of thiosemicarbazones (4–7) by treatment of 5-(morpholino- sulfonyl) isatin with thiosemicarbazides followed by cycloalkylation of the products with halogenated compounds to give the thiazole derivatives (8–19). Most of the synthesized compounds were screened against Gram (+), Gram (−) bacterial and fungi. The best gram positive activity was displayed by compounds 1, 13, 14, 15, 16 and 18 and the best gram negative bacteria was showed by compounds 1, 12, 13, 15, and 19, whereas compounds 1, 12, 13, 15, and 19 exhibited the best antifungal activity.

Key words

thiosemicarbazones - thiosemicarbazide - antibacterial and antifungal activities

• References

• 1 Abbas SY, El-Sharief MAMSh, Basyouni WM et al. Thiourea derivatives incorporating a hippuric acid moiety: Synthesis and evaluation of antibacterial and antifungal activities. Eur J Med Chem 2013; 64: 111-120
• 2 El-Sharief MAMSh, Abbas SY, El-Bayouki Kh AM et al Synthesis of thiosemicarbazones derived from N-(4-hippuric acid) thiosemicarbazide and different carbonyl compounds as antimicrobial agents. Eur J Med Chem 2013; 67: 263-268
• 3 Helal MH, Abbas SY, Salem MA et al. Synthesis and characterization of new types of 2-(6-methoxy-2-naphthyl)propionamide derivatives as potential antibacterial and antifungal agents. Med Chem Res 2013; 22: 5598-5609
• 4 Aly MM, Mohamed YA, El-Bayouki Kh AM et al. Synthesis and biological activity of some 4(3H)-quinazolinone-2-carboxaldehyde thiosemicarbazone and their metal complexes. Eur J Med Chem 2010; 45: 3365-3373
• 5 Abbas SY, Farag AA, Ammar YA et al. Synthesis, characterization, and antiviral activity of novel fluorinated isatin derivatives. Monatsh Chem 2013; 144: 1725-1733
• 6 Sriram D, Yogeeswari P, Gopal G. Synthesis, anti-HIV and antitubercular activities of lamivudine prodrugs. Eur J Med Chem 2005; 40: 1373-1376
• 7 Pandeya SN, Sriram D, Nath G et al. Synthesis, antibacterial, antifungal and anti-HIV activities of Schiff and Mannich bases derived from isatin derivatives and N-4-(4′-chlorophenyl)thiazol-2-yl] thiosemicarbazide. Eur J Pharm Sci 1999; 9: 25-31
• 8 Bondock S, Naser T, Ammar YA. Synthesis of some new 2-(3-pyridyl)-4,5-disubstituted thiazoles as potent antimicrobial agents. Eur J Med Chem 2013; 62: 270-279
• 9 Mehta DP, Sengar NPS, Pathak AK. 4-Thiazolidinone- a new profile of various pharmacological activities. Oriental J of Chem 2008; 24: 441-454
• 10 Farag AA, Abd-Alrahman SN, Ahmed GF et al. Synthesis of some azoles incorporating sulfonamide moiety as anticonvulsant agents. Arch Pharm 2012; 345: 703-712
• 11 El-Bayouki Kh AM, Basyouni WM, Mostafa EA et al. Synthesis, characterization and molluscicidal activity of Mn, Co, Ni and Cu metal complexes of ethyl 5-amino-2-(methylthio) thiazole-4-carboxylate. Synth React Inorg Met-Org 2014; 44: 537-540
• 12 Raparti V, Chitre T, Bothara K et al. Novel 4-(morpholin-4-yl)-N0-(arylidene) benzohydrazides: Synthesis, antimycobacterial activity and QSAR investigations. Eur J Med Chem 2009; 44: 3954-3960
• 13 Farrag AA, Ammar YA, El-Sehemi AG et al. Synthesis and anticancer activity of some fluorinated compounds containing quinoxaline moiety. Egyptian J biomed Sci 2010; 34: 13-25
• 14 Farag AA, Khalifa EM, Sadik NA et al. Synthesis, characterization and evaluation of some novel 4(3H)-quinazolinone derivatives as anti-inflammatory and analgesic agents. Med Chem Res 2013; 22: 440-452
• 15 Ivachtchenko AV, Khvat AV, Kobak VV et al. A new insight into the Pfitzinger reaction. A facile synthesis of 6-sulfamoylquinoline-4-carboxylic acids. Tetrahedron Lett 2004; 45: 5473-5476