• Kamilia M. Amin
  • Sahar M. Abou-seri
  • Rana M. Abdelnaby Pharmaceutical Chemistry Department, Faculty of Pharmacy, Misr University for Science and Technology, Al-Motamayez District, 6th of October City, Egypt
  • Heba S. Rateb
  • Mahmoud A. F. Khalil
  • Mohamed M. Hussein


Coumarin, Thiosemicarbazones, Thiazolidin-4-ones, Antimicrobial activity


Objective: Synthesize new series of 7-hydroxy-4-methylcoumarin and 7-alkoxy-4-methylcoumarin derivatives featuring thiosemicarbazone or thiazolidin-4-one moieties and to evaluate their antimicrobial activity against two strains of Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), two Gram-negative bacteria (Escherichia Coli and Pseudomonas aeruginosa), and Candida albicans.

Methods: Preparation of the new coumarin derivatives was done by adopting Pechmann condensation and attaching different isothiocyanates to give coumarin-thiosemicarbazone hybrids. Thiosemicarbazones were cyclized into thiazolidine-4-ones using chloroacetic acid or diethyl bromo malonate.

Results: Compounds VIb, Xb, XIVb, and XVc gave the highest inhibition zones (>20 mm) against Staphylococcus aureus. Their MIC (minimum inhibitory concentration) values ranging from 0.19-0.36 µg/ml were better than the reference drug tobramycin with MIC= 2µg/ml.

Conclusion: The newly synthesized compounds with the 7-hydroxyl group showed better antimicrobial activity than those with the 7-alkoxy groups.

Keywords: Coumarin, Thiosemicarbazones, Thiazolidin-4-ones, Antimicrobial activity


Download data is not yet available.


Jain PK, Himanshu J. Coumarin: chemical and pharmacological profile. J Appl Pharm Sci 2012;2:236-40.

Vahid V, Farhad H. Microwave assisted convenient one-pot synthesis of coumarin derivatives via pechmann condensation catalyzed by FeF3 under solvent-free conditions and antimicrobial activities of the products. Molecules 2014;19:13093-103.

Varughese MA, Ramakrishna PB, Shriniwas DS. Bismuth (III) nitrate pentahydrate—a mild and inexpensive reagent for the synthesis of coumarins under mild conditions. Tetrahedron Lett 2005;46:6957–9.

Borges F, Roleira F, Milhazes N, Santana L, Uriarte E. Simple coumarins and analogues in medicinal chemistry: occurrence, synthesis, and biological activity. Curr Med Chem 2005; 12:887-916.

Heiner GG, Fatima, Russell PK, Haase AT, Ahmad N, Mohammed N, et al. Field trials of methisazone as a prophylactic agent against smallpox. Am J Epidemiol 1971;94:435-49.

Sau DK, Butcher RJ, Chaudhuri S, Saha N. Spectroscopic, structural and antibacterial properties of copper(II) complexes with bio-relevant 5-methyl-3-formylpyrazole N-benzyl-N-methyl thiosemicarbazone Mol Cell Biochem 2003;253:21-9.

Pavan FR, da S Maia P, Leite SR, Deflon VM, Batista AA, Sato DN, et al. Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: anti–mycobacterium tuberculosis activity and cytotoxicity. Eur J Med Chem 2010;45:1898-905.

Magalhaes Moreira DR, De Oliveira AD, Teixeira de Moraes Gomes PA, De Simone CA, Villela FS, Ferreira RS, et al. Conformational restriction of aryl thiosemicarbazones produces potent and selective anti-Trypanosoma cruzi compounds which induce apoptotic parasite death. Eur J Med Chem 2014;75:467-78.

Afrasiabi Z, Sinn E, Chen JN, Ma YF, Rheingold AL, Zakharov LN, et al. Appended 1,2-naphthoquinones as anticancer agents 1: synthesis, structural, spectral and antitumor activities of ortho-naphthoquinone thiosemicarbazone and its transition metal complexes. Inorg Chim Act A 2004;357:271-8.

Sankaraperumal A, Karthikeyan J, Nityananda A, Lakshmi SR. Nickel (II) complex of p-[N, N-bis(2-chloroethyl) amino] benzaldehyde-4-methyl-thiosemicarbazone: Synthesis, characterization, and biological application. Polyhedron 2013; 50:264-9.

Patil S, Unki S, Kulkarni A, Naik V, Badami P. Co(II), Ni(II) and Cu(II) complexes with coumarin-8-yl Schiff-bases: spectroscopic, in vitro antimicrobial, DNA cleavage and fluorescence studies. Spectrochim Acta Part A 2011;79:1128-36.

Bondock S, Khalifa W, Fadda AA. Synthesis and antimicrobial evaluation of some new thiazole, thiazolidinone and thiazoline derivatives starting from 1-chloro-3, 4-dihydronaphthalene-2-carboxaldehyde. Eur J Med Chem 2007;42:948-54.

Sandhu S, Bansal Y, Silakari O, Bansal G. Coumarin hybrids as novel therapeutic agents. Bioorg Med Chem 2014;15:3806-14.

Ronad PM, Noolvi MN, Sapkal S, Dharbhamulla S, and Maddi VS. Synthesis and antimicrobial activity of 7-(2-substituted phenylthiazolidinyl)-benzopyran-2-one derivatives. Eur J Med Chem 2010;45:85-9.

Bojan Š, Maja M, Milan C, Lars G. 4-Methyl-7-hydroxycoumarin antifungal and antioxidant activity enhancement by substitution with thiosemicarbazide and thiazolidinone moieties. Food Chem 2013;139:488–95.

Ali P, Jyotsna M, Vandana T, Javed S, Rajendra D, Moulay HY, et al. Pharmacophores modeling in terms of prediction of theoretical physicochemical properties and verification by experimental correlations of novel coumarin derivatives produced via Betti’s protocol. Eur J Med Chem 2010;45:4370-8.

Pechmann HV, Duisberg C. Uber die verbindungen der phenole mit acetessigather. Ber Dtsch Chem Ges 1883;16:2119–28.

Chakraborti A, Gulhane R, Shivani. Copper (II) tetrafluoroborate-catalyzed acetylation of phenols, Thiols, Alcohols­, and amines. Synthesis 2004;1:111-5.

Valery F Traven. New synthetic routes to furocoumarins and their analogs: a review. Molecules 2004;9:50-66.

Alexander Williamson. XLV. Theory of etherificationâ€. Philos Mag 1850;37:350-6.

Smith PAS, Most EE Jr. Quaternary hydrazones and their rearrangement. J Org Chem 1957;22:358-62.

Newkome GR, Fishel DL. Synthesis of simple hydrazones of carbonyl compounds by an exchange reaction. J Org Chem 1966;31:677-81.

Mohamad MM, Hussein. Synthesis, photosensitizing and antimicrobial studies on coumarin thiosemicarbazones. Al-Azhar J Pharm Sci 2009;39-55.

Shiva PS, Surendra SP, Krishna R, Virgil IS. Chemistry and biological activity of thiazolidinones. Chem Rev 1981;81:175-203.

Mashooq AB, Nadeem S, Suroor AK, Mohamed IM. Synthesis of triazolothiazolidinone derivatives of coumarin with antimicrobial activity. Acta Pol Pharm 2009;66:625-32.

Naceur H, Abdullah SA, Ridha B, Alary F. Synthesis and characterization of new thiazolidinones containing coumarin moieties and their antibacterial and antioxidant activities. Molecules 2012;17:9321-34.

Salmon SA, Watts JL, Aarestrup FM, Pankey JW, Yancey RJ Jr. Minimum inhibitory concentrations of selected antimicrobial agents against organisms isolated from the mammary glands of dairy heifers in New Zealand and Denmark. J Dairy Sci 1998;81:570-8.



How to Cite

Amin, K. M., S. M. Abou-seri, R. M. Abdelnaby, H. S. Rateb, M. A. F. Khalil, and M. M. Hussein. “SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL COUMARIN DERIVATIVES AS POTENTIAL ANTIMICROBIAL AGENTS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 4, Apr. 2016, pp. 109-16,



Original Article(s)