• Nabila A. Kheder King Khalid University
  • Farag M. A. Altalbawy Department of Measurements and Environmental Applications, National Institute of Laser Enhanced Sciences (NILES), Cairo University, Giza, Egypt


Objective: Synthesis of some novel bis [3-(aryl)-2-cyanoacrylamide], bis-pyrazole, bis-thiazole and bis-triazole derivatives starting from N,N'-ethane-1,2-diylbis(2-cyanoacetamide) (1) to evaluate for their in-vitro antibacterial, antifungal and anticancer activities.

Methods: Reaction of N, N'-ethane-1,2-diylbis(2-cyanoacetamide) (1) with different aromatic and heteroaromatic aldehydes yielded the corresponding bis[3-(aryl)-2-cyanoacrylamide] derivatives, which reacted with hydrazine hydrate to give N,N'-ethane-1,2-diylbis[3-amino-5-(4-aryl)-1H-pyrazole-4-carboxamide] derivatives. Compound 1 reacted with each of thioglycolic acid, Phenyl isocyanate and elemental sulfur in presence triethylamine to give bis-thiazole derivatives. Diazotization of 1 with the desired diazonium chloride yielded the bis-hydrazone derivatives. The latter compounds refluxed with hydroxylamine hydrochloride and chloro- acetonitrile to give bis-triazole and bis-pyrazole derivatives respectively.

Results: The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR, [13]C NMR and mass spectral data. A total fourteen new synthesized compounds were evaluated for their in-vitro antibacterial, antifungal and anticancer activities against human liver cancer cell line (HEPG-2).

Conclusion: The results obtained indicated that some of such compounds showed promising activities against Gram-positive, Gram-negative bacteria, fungi and anticancer activity in relation to the reference drugs ampicillin, gentamicin, Amphotericin B and vinblastine respectively.


Keywords: Bis-pyrazole, Bis-thiazole, Bis-triazole, Antibacterial and antifungal activities, Anticancer activity


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1. Rajendra PY, Lakshmana RA, Prasoona L, Murali K, Ravi KP. Synthesis and antidepressant activity of some 1,3,5-triphenyl-2-pyrazolines and 3-(2″-hydroxy naphthalen-1″-yl)-1,5-diphenyl-2-pyrazolines. Bioorg Med Chem Lett 2005;15:5030-4.
2. Özdemir Z, Kandilci HB, Gümüşel B, Caliş U, Bilgin AA. Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-furyl)-pyrazoline derivatives. Eur J Med Chem 2007;42:373-9.
3. Özdemir A, Turan-Zitouni G, Kaplancikli ZA, Revial G, Güven K. Synthesis and antimicrobial activity of 1-(4-aryl-2-thiazolyl)-3-(2-thienyl)-5-aryl-2-pyrazoline derivatives. Eur J Med Chem 2007;42:403-9.
4. Özdemir A, Gürsoy A, Demirayak S, Capan G, Erol K, Vural K. Synthesis and preliminary evaluation of new 5-pyrazolinone derivatives as analgesic agents. Eur J Med Chem 2000;35:359-64.
5. Brzozowski Z, Czewski FS, Gdaniec M. Synthesis, structural characterization and antitumor activity of novel 2,4-diamino-1,3,5-triazine derivatives. Eur J Med Chem 2000;35:1053-64.
6. Jeong TS, Kim KS, An S, Cho KH, Lee S, Lee WS. Novel 3,5-diaryl pyrazolines as human acyl-CoA: cholesterol acyltransferase inhibitors. Bioorg Med Chem Lett 2004;14:2715-7.
7. Mishra R, Tomer I, Priyanka N, Sharma K, Jha KK. Synthesis and antimicrobial evaluation of some novel thiazole derivatives. Pharm Sin 2012;3:361-6.
8. Argyropoulou I, Geronikaki A, Vicini P, Zani F. Synthesis and biological evaluation of sulfonamide thiazole and benzothiazole derivatives as antimicrobial agents (HP-3516MP). Arkivoc 2009;6:89-102.
9. Sharma RN, Xavier FP, Vasu KK, Chaturvedi SC, Pancholi SS. Synthesis of 4-benzyl-1,3-thiazole derivatives as potential anti-inflammatory agents: An analogue-based drug design approach. J Enzyme Inhib Med Chem 2009;24:890-7.
10. Jaishree V, Ramdas N, Sachin J, Ramesh BJ. in vitro antioxidant properties of new thiazole derivatives. J Saudi Chem Soc 2012;16:371-6.
11. Franklin PX, Yerande S, Thakar HM, Inamdar GS, Giri RS, Padh H, et al. Synthesis, anti-inflammatory and HIV-1 integrase inhibitory activities of 1,2-bis[5-thiazolyl]ethane-1,2-dione derivatives. Indian J Pharm Sci 2009;71:259-73.
12. Hargrave KD, Hess FK, Oliver JT. N-(4-Substituted-thiazolyl)oxamic acid derivatives, new series of potent, orally active antiallergy agents. J Med Chem 1983;26:1158-63.
13. Al-Soud YA, Al-Masoudi NA, Ferwanah AS. Synthesis and properties of new substituted 1,2,4-triazoles: potential antitumor agents. Bioorg Med Chem 2003;11:1701-8.
14. Al-Soud YA, Al-Dweri MN, Al-Masoudi NA. Synthesis, antitumor and antiviral properties of some 1,2,4-triazole derivatives. Farmaco 2004;59:775-83.
15. Moise M, Sunel V, Profire L, Popa M, Desbrieres J, Peptu C. Synthesis and biological activity of some new 1,3,4-thiadiazole and 1,2,4-triazole compounds containing a phenylalanine moiety. Molecules 2009;14:2621-31.
16. Buckle DR, Rockell CJ, Smith H, Spicer BA. Studies on 1,2,3,-triazoles. 10. Synthesis and antiallergic properties of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazoles and their s-oxides. J Med Chem 1984;27:223-7.
17. Eison AS, Eison MS, Torrente DP, Wright RN, Yocca FD. preclinical pharmacology of a new antidepressant. Psychopharmacol Bull 1990;26:311-5.
18. Öncü S, Punar M, Eraksoy H. Comparative activities of β-lactam antibiotics and quinolones for invasive streptococcus pneumoniae isolates. Chemotherapy 2004;50:98-100.
19. Altalbawy FMA. Synthesis and antimicrobial evaluation of some novel bis-α,β-unsaturated ketones, nicotine nitrile, 1,2-dihydropyridine-3-carbonitrile, fused thieno[2,3-b]pyridine and pyrazolo[3,4-b]pyridine derivatives. Int J Mol Sci 2013;14:2967-79.
20. Altalbawy FMA, Darwish ESS. Synthesis and antimicrobial activity of 1,2,4-triazolo[4,3-b][1,2,4,5]tetrazines. Asian J Chem 2011;23:2951-5.
21. Altalbawy FMA, Darwish ESS, Mahmoud FF. Synthesis and antimicrobial evaluation of some new pyrazole, fused pyrazolo[1,5-a]-pyrimidine and pyrazolo[1,5-d]pyrimido[4,5-d][1,2,3]triazine derivatives. Asian J Chem 2012;24:2997-3002.
22. Altalbawy FMA, Mohamed GG, Mohamed IAM. Synthesis, characterization and biological activity of some transition metals complexes with schiff base derived from 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol and p-methoxysalicyldehyde. Asian J Chem 2010;22:7291-307.
23. Altalbawy FMA, Mohamed GG, Sayed MAE, Mohamed IA. Synthesis, characterization, and biological activity of some transition metal complexes with Schiff base ligands derived from 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol and salicylaldehyde. Monatshefte Fur Chemie 2012;143:79-89.
24. Kheder NA. Convenient synthesis of novel bis(hydrazone) and bis(indole) derivatives. Heterocycles 2009;78:1281-8.
25. Mabkhoot YN, Kheder NA, Al-Majid AM. Facile and convenient synthesis of new thieno[2,3-b]-thiophene derivatives. Molecules 2010;15:9418-26.
26. Kheder NA, Mabkhoot YN. Synthesis and antimicrobial studies of some novel bis-[1,3,4]thiadiazole and bis-thiazole pendant to thieno[2,3-b]thiophene moiety. Int J Mol Sci 2012;13:3661-70.
27. Kheder NA, Riyadh SM, Asiry AM. Azoles and bis-azoles: synthesis and biological evaluation as antimicrobial and anti-cancer agents. Chem Pharm Bull 2013;61:504-10.
28. Farag AM, Kheder NA, Budesinsky M. Regioselective synthesis of polysubstituted 3,3′-bi-1H-pyrazole derivatives via 1,3-dipolar cycloaddition reactions. Tetrahedron 1997;53:9293-300.
29. Kheder NA, Mabkhoot YN, Farag AM. Synthesis and antimicrobial evaluation of some bis (thioxopyridine), bis (pyrazolo [3, 4-b] pyridine), bis (thieno [2, 3-b] pyridine), bis (1, 3, 4-thiadiazole) and bis-thiophene derivatives. Heterocycles 2008;75:2937-48.
30. Kheder NA. Synthesis of some novel bis (pyrazole), bis (pyridine) and bis (pyrazolo [5, 1-c]-1, 2, 4-triazine derivatives. Heterocycles 2009;78:1815-22.
31. Butler RN. Diazotization of heterocyclic primary amines. Chem Rev 1975;75:241-57.
32. Esmail R, Kurzer F. Heterocyclic compounds from urea derivatives. Part XXIII. Thiobenzoylated thiocarbonohydrazides and their cyclization. J Chem Soc Perkin Trans 1 1975;18:1787-91.
33. Muanz DN, Kim BW, Euler KL, Williams L. Antibacterial and antifungal activities of nine medicinal plants from Zaire. Int J Pharmacogn 1994;32:337-45.
34. Harborne JB, liams CAA. Recent advances in the chemosystematics of the monocotyledons. Phytochemistry 1994;37:3-18.
35. Vijayan P, Raghu C, Ashok G, Dhanaraj SA, Suresh B. Antiviral activity of medicinal plants of nilgiris. Indian J Med Res 2004;120:24-9.
36. Al-Matar HM, Riyadh SM, Elnagdi MH. Studies with enamines: reactivity of N, N-dimethyl-N-[(E)-2-(4-nitrophenyl)-1-ethenyl] amine towards nitrilimine and aromatic diazonium salts. J Heterocycl Chem 2007;44:603-7.
37. Darwish ES, Kheder NA, Farag AM. Synthesis and antimicrobial evaluation of some new pyridine based heterocycles. Heterocycles 2010;81:2247-56.
38. Kheder NA, Mabkhot YN, Farag AM. A convenient access to new pyrido [4, 3-d] pyrimidine, thiazolo [3, 4-c] pyrimidine and pyrimido [4, 5-d] pyridazine derivatives. Arkivoc 2008;17:107-16.
39. Child RG, Wilkinson RG, Tomcu-Fucik A. Effect of the substrate orientation of the adhesion of polymer joints. Chem Abstr 1997;87:6031.
40. Garg HG, Praksh C. Potential antidiabetics, 11. Preparation of 4-arylazo-3,5-disubstituted-(2H)-1,2,6-thiadiazine 1,1-dioxides. J Med Chem 1972;15:435-6.
41. Browing CH, Cohen JB, Ellingworth S, Gulbransen R. The antiseptic properties of the amino derivatives of styryl and anil quinoline. J Storage 1926;100:293-325.
42. Swati, Ginni, Karnawat R, Sharma IK, Verma PS. Synthesis, characterisation and antimicrobial screening of some azo compounds. Int J Appl Biol Pharm Technol 2011;2:332-8.
43. Goyal NR, Verma MS, Singhal NK. Voltammetric investigations of the reduction of direct orange-31 a bisazo dye. Croat Chem Acta 1998;71:715-26.
44. Hamzacebi MC, Rollas S, Küçükgüzel SG, Kaymakçıoğlu BK. Synthesis and structure elucidation of hydrazones derived from N-(2, 4-dimethylphenyl)-3-oxobutanamide. Arkivoc 2008;12:188-94.
45. Darwish ES, Abdel fattah AM, Attaby FA, Al-Shayea ON. Synthesis and antimicrobial evaluation of some novel thiazole, pyridone, pyrazole, chromene, hydrazone derivatives bearing a biologically active sulfonamide moiety. Int J Mol Sci 2014;15:1237-54.
46. Farghaly TA, Mahmoud HK. Synthesis, tautomeric structures, and antitumor activity of new perimidines. Arch Pharm 2013; 346:392-402.
47. Shier WT. Mammalian cell culture on $5 a day. A laboratory manual of low-cost methods. university of the Philippines at los bafios publications, College, Laguna, Philippine; 1991.
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How to Cite
Kheder, N. A., and F. M. A. Altalbawy. “SYNTHESIS, IN VITRO ANTIMICROBIAL, ANTI-LIVER CANCER EVALUATION OF SOME NOVEL BIS-CYANOACRYLAMIDE AND BIS-AZOLES DERIVATIVES”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 1, Dec. 2015, pp. 420-7,
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