The Reaction of Cyanoacetylhdrazine with Furan-2-Aldehyde: Novel Synthesis of Thiophene, Azole, Azine and Coumarin Derivatives and Their Antitumor Evaluation

Wagnat W. Wardakhan, Sherif M. Sherif, Rafat M. Mohareb, Amr S. Abouzied

Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.
National Organization for Drug Control & Research, Cairo, Egypt.

DOI: 10.4236/ijoc.2012.24044                

Abstract

The reaction of cyanoacetylhydrazine 1 with furan-2-aldehyde 2 gives the hydrazide-hydrazone derivative 3. The latter compound undergoes a series of heterocyclization reactions to give new heterocyclic compounds. The antitumor evaluation of the newly synthesized products against three cancer cell lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) were recorded. Some of the synthesized compounds show high inhibitory effects.

Keywords

Acetylhydrazine; Hydrazide-Hydrazone; Thiophene; Thiazole; Pyridine; Coumarin; Antitumor

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	S. Rollas, N. Kalyoncuoglu, D. Sur-Altiner and Y. Yegenoglu, “5-(4-Aminophenyl)-4-substituted-2,4-dihydro-3H- 1,2,4-triazole-3-thiones: Synthesis and Antibacterial and Antifungal Activities,” Pharmazie, Vol. 48, No. 4, 1993, pp. 308-309. doi:10.1016/S0223-5234(99)80048-8
[2]	S. Papakonstantinou-Garoufalias, N. Pouli, P-Marakos and A. Chytyro-glouladas, “Synthesis Antimicrobial and Antifungal Activity of Some New 3-Substituted Derivatives of 4-(2,4-Dichlorophenyl)-5-adamantyl)-1H-1,2,4-triazole,” il Farmaco, Vol. 57, No. 12, 2002, pp. 973-977. doi:10.1002/chin.200314128
[3]	M. Kidwai, R. Kumar, A. Srivastava and H. P. Gupta, “Microwave-Assisted Synthesis of Novel 1,3,4-Thiadiazolyl-Substituted 1,2,4-Triazines as Potential Antitubercular Agents,” Bioorganic Chemistry, Vol. 26, No. 5, 1998, pp. 289-294. doi:10.1006/bioo.1998.1108
[4]	V. V. Kachhadia, M. R. Patel and H. S. Joshi, “Heterocyclic Systems Containing S/N Regioselective Nucleophilic Competition: Facile Synthesis, Antitubercular and Antimicrobial Activity of THIOHydantoins and Iminothiazolidinones Containing the Benzo[b]thiophene Moiety,” Journal of the Serbian Chemical Society, Vol. 70, No. 2, 2005, pp. 153-161. doi:10.1002/ardp.201000010
[5]	P. K. Kadaba, “Rational Drug Design and the Discovery of the Delta2-1,2,3-triazolines, a Unique Class of Anticonvulsant and Antiischemic Agents,” Current Medicinal Chemistry, Vol. 10, No. 20, 2003, pp. 2081-2108. doi:10.2174/0929867033456765
[6]	I. kücükgüzel, S. G. Kücükgüzel, S. Rollas, G. O.-Sanis, O. Ozdemir, I. Bayrak, T. Altug and J. P. Stables, “Synthesis of Some 3-(Arylalkylthio)-4-alkyl/aryl-5-(4-aminophenyl)-4H-1,2,4-triazole Derivatives and Their Anticonvulsant Activity,” Il Farmaco, Vol. 59, No. 11, 2004, pp. 893-901. doi:10.4103/0975-7406.80783
[7]	M. D. Mullican, M. W. Wilson, D. T. Connor, C. R. Kostlan, D. J. Schrier and R. D. Dyer, “Design of 5-(3,5- Di-tert-butyl-4-hydroxyl-phenyl)-1,3,4-thiadiazoles, -1,3,4- Oxadiazoles, and -1,2,4-Triazoles as Orally-Active, Nonulcerogenic Antiinflammatory Agents,” Journal of Medicinal Chemistry, Vol. 36, No. 8, 1993, pp. 1090-1099. doi:10.1021/jm00060a017
[8]	E. Palaska, G. ?ahin, P. Kelicen, N. T. Durlu and G. Altinok, “Synthesis and Anti-Inflammatory Activity of 1- Acylthiosemicarb-azides, 1,3,4-Oxadiazoles, 1,3,4-Thiadiazoles and 1,2,4-Triazole-3-thiones,” Il Farmaco, Vol. 57, No. 2, 2002, pp. 101-107. doi:10.1016/S0014-827X(01)01176-4
[9]	A.Varvaresou, T. Siatra-Papastaikoudi, A. Tsotinis, A. TsantiliKakoulidou and A. Vamvakides, “Synthesis, Lipophilicity and Biological Evaluation of Indole-Containing Derivatives of 1,3,4-Thiadiazole and 1,2,4-Triazole,” ?l Farmaco, Vol. 53, No. 5, 1989, pp. 320-326. doi:10.1016/S0014-827X(98)00024-X
[10]	B. S. Holla, B. Veerendra, M. K. Shivanada and B. Poojary, “Synthesis Characterization and Anticancer Activity Studies on Some Mannich Bases Derived from 1,2,4- Triazoles,” European Journal of Medicinal Chemistry, Vol. 38, No. 7-8, 2003, pp. 759-767. doi:10.1016/S0223-5234(03)00128-4
[11]	J. H. Lange, H. H. Stuivenberg, H. K. Coolen, T. J. Adolfs, A. C. McCreary, H. G. Keizer, H. C. Wals, W.Veerman, A. J. Borst, W. de Looff, P. C. Verveer and C. G. Kruse, “Bioisosteric Replacements of the Pyrazole Moiety of Rimonabant: Synthesis, Biological Properties, and Molecular Modeling Investigations of Thiazoles, Triazoles, and Imidazoles as Potent and Selective CB1 Cannabinoid Receptor Antagonists,” Journal of Medicinal Chemistry, Vol. 48, No. 6, 2005, pp. 1823-1838. doi:10.1021/jm040843r
[12]	R. M. Mohareb, H. Z. Shams and S. I. Aziz, “Novel Synthesis of 4-(Coumarin-3-yl)-1,3-thiazole, 2-(Coumarin-3- carbonyl)thieno(2,3-b)pyridine and 2-(Coumarin-3-carbonyl)thiophene Derivatives,” Sulfur Letters, Vol. 13, No. 3, 1991, pp. 101-110. doi:10.1002/chin.199238159
[13]	R. M. Mohareb, H. Z. Shams and Y. M. Elkholy, “The Use of 4-Phenyl-3-thiosemicarbazide in Heterocyclic Synthesis: Novel Synthesis of Thiazole, Pyrazole and 1,3,4- Thiadiazine Derivatives,” Phosphorus, Sulfur & Silicon, Vol. 72, No. 4, 1992, pp. 93-102. doi:10.1002/chin.199319192
[14]	H. Z. Shams, Y. M. Elkholy, N. S. Ibrahim and M. H. Elnagdi, “Nitriles in Organic Synthesis: New Routes for Synthesis of Pyridines and Azinothiopyrans,” Journal für Praktische Chemie, Vol. 330, No. 5, 1988, 817-819. doi:10.1002/prac.19883300521
[15]	S. M. Sherif, R. M. Mohareb, H. Z. Shams and H. M. Gaber, “A Convenient Synthesis of Polyfunctionally Substituted Benzo[b]thiophen-2-yl-pyrimidine,-pyrazole,-isoxazole and Pyridazine Derivatives,” Journal of Chemical Research, Vol. 1995, 1995, pp. 434-435, 2658-2674.
[16]	H. Z. Shams, Y. M. Elkholy, R. A. Azzam and R. M. Mohareb, “Synthetic Potentialities of Thiophene Systems in Heterocyclic Synthesis: Anovel Synthesis of Thieno[2,3-b]pyridine Derivatives,” Phosphorus, Sulfur & Silicon, Vol. 155, No. 2, 1999, pp. 215-233. doi:10.1080/10426509908044972
[17]	W. W. Wardakhan, H. Z. Shams and H. E. Moustafa, “Synthesis of Polyfunctionally Substituted Thiophene, Thieno[2,3-b]pyridine and Thieno[2,3-d]pyrimidine Derivatives,” Phosphorus, Sulfur & Silicon, Vol. 180, No. 8, 2005, pp. 1815-1827. doi:10.1080/104265090889422