Login Register Cart 0
Generic placeholder image

Current Organic Synthesis

Editor-in-Chief

ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis of New Cyanopyridine Scaffolds and their Biological Activities

Author(s): Nabil A. Alhakamy, Ahmad O. Noor, Khaled M. Hosny, Jenny Jeehan Nasr, Moustafa M.G. Fouda, Tawfik A. Khattab* and Hatem E. Gaffer

Volume 17, Issue 7, 2020

Page: [567 - 575] Pages: 9

DOI: 10.2174/1570179417666200628020602

Price: $65

Abstract

Background: 3-Cyanopyridine analogues are significant moieties with a variety of biological effects such as antioxidant, antimicrobial, anti-inflammatory and cytotoxic agents. In addition, they could be applied in the treatment of several diseases.

Objective: The study conducted cyclo-addition of 3a-e derivatives with malononitrile to yield the corresponding 6-(4-((3-cyano-pyridinyl) amino) phenyl)-4-phenylnicotinonitriles 4a-e.

Materials and Methods: Physical and spectral analyses were performed to demonstrate the proper structures of all incorporated analogues. The in vitro antimicrobial activity of the preps derivatives was investigated by testing them with a panel of pathogenic strains of bacteria and fungi. The anti-tuberculosis activity was observed against the Mycobacterium tuberculosis H37Rv strain. When examining cytotoxic agents for four different cell lines, researchers found that their activity was persuasive compared with that of standard antibiotics. In addition, the antioxidant activity of the synthesized analogues was evaluated using the DPPH method.

Results and Discussions: The synthesized analogues were examined to determine their activity against the M. tuberculosis H37Rv strain. Derivatives 2c, 2e, 3d and 3e had good inhibition. Further screening was done for the highest potency against M. tuberculosis to determine the MICs. The antioxidant efficacy was evaluated via the DPPH technique matched with vitamin C as a positive control. The prospective results showed that the derivatives did not display scavenging efficacies in comparison with the standard.

Conclusion: Some synthesized derivatives displayed good potency against bacterial activity and M. Tuberculosis. However, the antioxidant performance of these derivatives did not display scavenging efficacies compared to vitamin C. The cytotoxic activity of the synthesized derivatives was examined against various cell lines to display good cytotoxic activity in the order 4a-e > 2a-e > 3a-b.

Keywords: 3-cyanopyridine, anti-tuberculosis, anticancer activity, antimicrobial, antioxidant, cytotoxicity.

« Previous Next »
Graphical Abstract

[1]
Wang, C. Synthesis and biological evalution of terahydrobenzo[b]pyran derivaitves as potential anti-ovarian cancer agents. Biomed. Res., 2016, (Special Issue), S322-S325.
[2]
Hafez, H.N.; Alshammari, A.G.; El-Gazzar, A.R. Facile heterocyclic synthesis and antimicrobial activity of polysubstituted and condensed pyrazolopyranopyrimidine and pyrazolopyranotriazine derivatives. Acta Pharm., 2015, 65(4), 399-412.
[http://dx.doi.org/10.1515/acph-2015-0037] [PMID: 26677897]
[3]
El-Agrody, A.M.; El-Hakim, M.H.; Abd El-Latif, M.S.; Fakery, A.H.; El-Sayed, E.M.; El-Ghareb, K.A.A. Synthesis of pyrano[2,3-D]pyrimidine and pyrano[3,2-E][1,2,4]-triazolo[2,3-C]pyrimidine derivatives with promising antimicrobial activities. acta Pharm, 2000, 50, 111-120.
[4]
Safari, F.; Hosseini, H.; Bayat, M.; Ranjbar, A. Synthesis and evalution of antimicrobial activity, cytotoxic and pro-apoptotic effects of novel spiro-4H-pyran derivatives. RSC Advances, 2019, 9, 24843-24851.
[http://dx.doi.org/10.1039/C9RA03196K]
[5]
Joy, M.; Chakraborty, K. First report of two new antioxidative meroterpeno 2H-pyranoids from short-necked yellow-foot clam Paphia malabarica (family: Veneridae) with bioactivity against pro-inflammatory cyclooxygenases and lipoxygenase. Nat. Prod. Res., 2017, 31(6), 615-625.
[http://dx.doi.org/10.1080/14786419.2016.1209670] [PMID: 27471883]
[6]
Mohareb, R.M.; Abdo, N.Y.M.; Al-Farouk, F.O. Synthesis, cytotoxic and anti-proliferative activity of novel thiophene, thieno[2,3-b]pyridine and pyran derivatives derived from 4,5,6,7-tetrahydrobenzo[b]thiophene derivative. Acta Chim. Slov., 2017, 64(1), 117-128.
[http://dx.doi.org/10.17344/acsi.2016.2920] [PMID: 28380235]
[7]
Faghih, Z.; Faghih, Z.; Diver, M.; Khabnadideh, S. Cytotoxic activity of some spirooxidole-4h-pyran derivatives. J. Pharm. Res. Int., 2019, 31(6), 1-6.
[http://dx.doi.org/10.9734/jpri/2019/v31i630364]
[8]
Hammouda, M.A.A.; El-hag, F.A.A.; El-serwy, W.S.; El-Manawaty, M.A. Synthesis and characterization of new fused 4h-pyranquinoline carbonitrile derivatives with anticipated antitumor biological activity. RJPBCS, 2015, 6(1), 200-208.
[9]
Amr, A.E.; Maigali, S.S.; Abdulla, M.M. Synthesis, and analgesic and antiparkinsonian activeities of thiopyrimidine, pyrane, pyrazoline, and thiazolopyrimidine derivatives from 2-chloro-6-ethoxy-4-acetylpyridine. Monatsh. Chem., 2008, 139, 1409-1415.
[http://dx.doi.org/10.1007/s00706-008-0937-x]
[10]
Mohareb, R.M.; Zaki, M.Y.; Abbas, N.S. Synthesis, anti-inflammatory and anti-ulcer evaluations of thiazole, thiophene, pyridine and pyran derivatives derived from androstenedione. Steroids, 2015, 98, 80-91.
[http://dx.doi.org/10.1016/j.steroids.2015.03.001] [PMID: 25759119]
[11]
Saigal; Irfan, M.; Khan, P.; Abid, M.; Khan, M.M. Design, synthesis, and biological evaluation of novel fused spiro-4h-pyran derivatives as bacterial biofilm disruptor. ACS Omega, 2019, 4(16), 16794-16807.
[http://dx.doi.org/10.1021/acsomega.9b01571] [PMID: 31646225]
[12]
Aytemir, M.D.; Calis, U. Synthesis of some new hydroxypyranone derivatives and evalution of their anticonvulsant activities. FABAD J. Pharm. Sci., 2006, 31, 23-29.
[13]
Mahdavi, S.M.; Habibi, A.; Dolati, H.; Shahcheragh, S.M.; Sardari, S.; Azerang, P. Synthesis and antimicrobial evaluation of 4H-pyrans and schiff bases fused 4H-pyran derivatives as inhibitors of Mycobacterium bovis (BCG). Iran. J. Pharm. Res., 2018, 17(4), 1229-1239.
[PMID: 30568683]
[14]
Abdel Reheim, M.A.M.; Abdel Hafiz, I.S.; Elian, M.A. Pyrimidinethione as a building block in heterocyclic synthesis: Synthesis of pyrano[2,3-d]pyrimidine, chromeno[2,3-d]pyrimidine, pyrido[3′,2′:5,6]pyrano[2,3-b]pyridine and pyrimido[5′,4′:5,6]pyrano[2,3-d]pyrimidine derivatives. Heterocycl. Commun., 2016, 22(6), 311-317.
[http://dx.doi.org/10.1515/hc-2016-0039]
[15]
El-Gaby, M.S.A.; Abdel-Gawad, S.M.; Ghorab, M.M.; Heiba, H.I.; Aly, H.M. Synthesis and Biological Activity of Some Novel Thieno[2,3-b]quinoline, Quinolino[3′,2′:4,5]thieno[3,2-d]pyrimidine and Pyrido[2′,3′:4,5]thieno[2,3-b]quinoline Derivatives. Phosphorus Sulfur Silicon Relat. Elem., 2006, 181, 279-297.
[http://dx.doi.org/10.1080/104265090970322]
[16]
Al-Issa, S.A. Synthesis of a new series of pyridine and fused pyridine derivatives. Molecules, 2012, 17(9), 10902-10915.
[http://dx.doi.org/10.3390/molecules170910902] [PMID: 22968474]
[17]
El-Sharkawy, K.A.; El-Sayed, N.N.E.; Zaki, M. Uses of 2-amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile in the synthesis of heterocyclic compounds with anticonvulsant, behavioral and CNS antidepressant activities. Int. Res. J. Pure Appl. Chem., 2012, 2(1), 91-104.
[http://dx.doi.org/10.9734/IRJPAC/2012/1222]
[18]
Eid, F.A. Abd el-wahab A.H.F.; El-Hag Ali G.A.M.; Khafagy M.M. Synthesis and antimicrobial evalution of naphtha[2,1-b]pyrano[2,3-d]pyrimidine and pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives. Acta Pharm., 2004, 54, 13-26.
[PMID: 15050041]
[19]
Gaber, H.M.; Sherif, S.M.; Abu-Shanab, F.A. Studies on heterocyclic β-enaminonitriles: Synthesis of new condensed thieno[2,3-b]pyridines containing N-heterocyclic moieties. J. Sulfur Chem., 2005, 26(4-5), 393-403.
[http://dx.doi.org/10.1080/17415990500303255]
[20]
Badwy, M.A.; Abdel-Hady, S.A.; Eid, M.M. New heterocyclic synthesis, convenient synthesis of fused pyrimidines, pyrazoles, and triazines. J. Islam. Acad. Sci., 1989, 2(4), 241-243.
[21]
Sherif, S.M.; Hussein, A.M. Synthesis with heterocyclic β-enaminonitriles: an expeditious synthetic approach to polyfunctionally substituted 5-phenylsulfonylthiophenes and their fused derivatives. Monatsh. Chem., 1997, 128, 687-696.
[http://dx.doi.org/10.1007/BF00807600]
[22]
Fadda, A.A.; Adel-rahman, A.A.H.; Hamed, E.A.; Khalil, E.H. Utility of enaminonitriles in heterocyclic synthesis: synthesis and antimicrobial activity of some new azole and azine derivatives. American. J. Org. Chem., 2012, 2(2), 7-13.
[http://dx.doi.org/10.5923/j.ajoc.20120202.02]
[23]
Elmegeed, G.A.; Ahmed, H.H.; Hussein, J.S. Novel synthesized aminosteroidal heterocycles intervention for inhibiting iron-induced oxidative stress. Eur. J. Med. Chem., 2005, 40(12), 1283-1294.
[http://dx.doi.org/10.1016/j.ejmech.2005.07.012] [PMID: 16154236]
[24]
Mohammed, F.K.; Soliman, A.Y.; Sawy, A.; Badre, M.G. 2-Amino-5-hydroxy-4-phenyl-7-methyl-4H[1-chromeno-3-carbonitrile as a key precursor for the synthesis of several chromene based heterocyclic systems. J. Chem. Pharm. Res., 2009, 1(1), 213-224.
[25]
El-Assiery, S.A.; Sayed, G.A.; Fouda, A. Synthesis of some new annulated pyrazolo-pyrido (or pyrano) pyrimidine, pyrazolopyridine and pyranopyrazole derivatives. Acta Pharm., 2004, 54(2), 143-150.
[PMID: 15274757]
[26]
Salman, A.S.S. Synthesis and reaction of fused polynuclear heterocycles. Commun. Fac. Sci. Univ. Ank. Series B., 1999, 45, 85-91.
[http://dx.doi.org/10.1501/Commub_0000000384]
[27]
Bondock, S.; Fadaly, W.; Metwally, M.A. Enaminonitrile in heterocyclic synthesis: synthesis and antimicrobial evaluation of some new pyrazole, isoxazole and pyrimidine derivatives incorporating a benzothiazole moiety. Eur. J. Med. Chem., 2009, 44(12), 4813-4818.
[http://dx.doi.org/10.1016/j.ejmech.2009.07.024] [PMID: 19683840]
[28]
Behbehani, H.; Ibrahim, H.M.; Makhseed, S.; Elnagdi, M.H.; Mahmoud, H. 2-Aminothiophenes as building blocks in heterocyclic synthesis: synthesis and antimicrobial evaluation of a new class of pyrido[1,2-a]thieno[3,2-e]pyrimidine, quinoline and pyridin-2-one derivatives. Eur. J. Med. Chem., 2012, 52, 51-65.
[http://dx.doi.org/10.1016/j.ejmech.2012.03.004] [PMID: 22464424]
[29]
Radwan, M.A.A.; El-Sherbiny, M. Synthesis and antitumor activity of indolylpyrimidines: Marine natural product meridianin D analogues. Bioorg. Med. Chem., 2007, 15(3), 1206-1211.
[http://dx.doi.org/10.1016/j.bmc.2006.11.023] [PMID: 17157024]
[30]
Khalil, K.D.; Al-Matar, H.M.; Dorri, D.M.; Elnagdi, M.H. Studies with enaminones and enaminonitriles: Synthesis of 3-aroyl and 3-heteroaroyl-pyrazolo-[1,5-a]pyrimidines. Tetrahedron, 2009, 65, 9421-9427.
[http://dx.doi.org/10.1016/j.tet.2009.08.084]
[31]
Murray, P.R.; Baron, E.J.; Pfaller, M.A.; Tenover, F.C.; Yolken, R.H. GL wood, JA Washington (Eds.), Manual of Clinical Microbiology, Am. Soc. Microbiol., Washington, DC; , 1995.
[32]
Jones, R.N.; Barry, A.L.; Gavan, T.L.; Washington, I.I.A. Manual of Clinical Microbiology, fourth edn, Am. Soc. Microbiol. (1972), Washington DC , 1985.

Rights & Permissions Print Cite
Article Metrics
13
© 2024 Bentham Science Publishers | Privacy Policy