Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Author(s): Zeinab A. Muhammad, Fatimah Alshehrei, Mohie E.M. Zayed, Thoraya A. Farghaly* and Magda A. Abdallah

DOI: 10.2174/1389557519666190313095545

DownloadDownload PDF Flyer Cite As
Synthesis of Novel Bis-pyrazole Derivatives as Antimicrobial Agents

Page: [1276 - 1290] Pages: 15

  • * (Excluding Mailing and Handling)

Abstract

Background: bis-heterocycles especially those containing pyrazole moiety display much better antibacterial activity than mono heterocycles.

Objective: Herein, we synthesised a series of new bis-pyrazoles and investigated their antimicrobial agents.

Methods: A novel series of bis-pyrazole derivatives have been synthesized in good yield by coupling reaction of cyanoacetic acid {4-[(2-cyano-acetyl)-hydrazonomethyl]-benzylidene}-hydrazide with a number of diazonium salts of aromatic amines in DMF in the presence of NaOH. Refluxing of the produced hydrazones with hydrazine-hydrate in ethanolic solution afforded the respective bis-pyrazoles. On the other hand, the reaction of bis(cyanoacetic acid hydrazide) derivative with a diversity of hydrazonoyl chlorides in dioxane under reflux gave bis-pyrazoles.

Results: The structures of all the products were discussed and assured from all possible spectral data as well as for the elemental analysis. In addition, the results of the antimicrobial activity examination of selected derivatives revealed a high strength of some tested compounds compared to standard bactericides and fungicides utilized. Molecular docking of the newly synthesized compounds into the Enoyl ACP reductase active site supported the in vitro antimicrobial activity. All the tested compounds could fit in the enzyme binding pocket with significant binding affinities (-7.040 to -9.141 Kcal/mol).

Conclusion: The good results of the antimicrobial examination of the newly synthesized bis-pyrazoles comprise the considerable evidence of the importance of bis-heterocyclic compounds which encourages us to continue designing and synthesising a novel series with potent biological activity in the future.

Keywords: Antimicrobial agents, bis-pyrazoles, hydrazonoyl halides, coupling reaction, diazonium salts, hydrozones.

Graphical Abstract

[1]
Todar, K. Textbook of Bacteriology; Madison, WI, 2011.
[2]
Kheder, N.A.; Farghaly, T.A. Bis-hydrazonoyl chloride as precursors for synthesis of novel polysubstituted bis-azoles. Arab. J. Chem., 2017, 10, S3007-S3014.
[3]
Abdallah, M.A.; Farghaly, T.A.; Gaber, H.M.; Mabkhot, Y.N.; Muhammad, Z.A. Unexpected hydrazinolysis and antimicrobial activity of 3-[2-aryl-2-oxoethyl]-pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]-triazines. Curr. Org. Syn., 2017, 14(7), 1059-1066.
[4]
Mabkhot, Y.N.; Kaal, N.A.; Alterary, S.; Al-Showiman, S.S.; Farghaly, T.A.; Mubarak, M.S. Antimicrobial activity of thiophene derivatives derived from ethyl (E)-5-(3-dimethylamino) acryloyl)-4-methyl-2-(phenylamino)thiophene-3-carboxylate. Chem. Central. J., 2017, 11, 75.
[5]
Farghaly, T.A.; Abdallah, M.A.; Masaret, G.S.; Muhammad, Z.A. New and efficient approach for synthesis of novel bioactive [1, 3, 4] thiadiazoles incorporated with 1, 3-thiazole moiety. Eur. J. Med. Chem., 2015, 320-333.
[6]
Mahran, A.M.; Farghaly, T.A.; Nada, A.A. Hydrazonoyl halides in heterocycles: Synthesis and anti-microbial activity of new 1, 2, 4-benzotriazine and bis-1, 2, 4-benzotriazine derivatives. Res. Chem. Intermed., 2015, 41, 2961-2969.
[7]
Farghaly, T.A.; Mahmoud, H.K. Site and regioselectivity of the reaction of hydrazonoyl chlorides with perimidine-ketene aminal. Antimicrobial evaluation of the products. J. Heterocycl. Chem., 2015, 52, 86-91.
[8]
El-Gamel, N.E.A.; Farghaly, T.A. Design and synthesis of novel complexes containing N-phenyl-1H-pyrazole moiety: Ni complex as potential antifungal and anti-proliferative compound. Spectrochimica Acta Part A: Mol. Biomol. Spectroscop.., 2013, 115, 469-475.
[9]
Farghaly, T.A.; Hassaneen, H.M.E. Synthesis of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-ones 3 as potential antimicrobial agents. Arch. Pharmacal. Res., 2013, 36, 564-572.
[10]
Muhammad, Z.A.; Masaret, G.S.; Amin, M.M.; Abdallah, M.A.; Farghaly, T.A. Anti-inflammatory, analgesic and anti-ulcerogenic activities of novel bis-thiadiazoles, bis-thiazoles and bis-formazanes. Med. Chem., 2017, 13, 226-238.
[11]
Soural, M.; Bouillon, I.; Krchňák, V. Combinatorial libraries of bis-heterocyclic compounds with skeletal diversity. J. Comb. Chem., 2008, 10, 923-933.
[12]
Csuk, R.; Barthel, A.; Raschke, C.; Kluge, R.; Stroehl, D.; Trieschmann, L.; Boehm, G. Synthesis of monomeric and dimeric acridine compounds as potential therapeutics in alzheimer and prion diseases. Arch. Pharm., 2009, 342, 699-709.
[13]
Salama, S.K.; Mohamed, M.F.; Darweesh, A.F.; Elwahy, A.H.M.; Abdelhamid, I.A. Molecular docking simulation and anticancer assessment on human breast carcinoma cell line using novel bis(1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile) and bis(1,4-dihydropyrazolo[4′,3′:5,6]pyrano[2,3-b]pyridine-6-carbonitrile) derivatives. Bioorg. Chem., 2017, 71, 19-29.
[14]
Ibrahim, N.S.; Mohamed, M.F.; Elwahy, A.H.M.; Abdelhamid, I.A. Biological activities and docking studies on novel bis 1,4-DHPS linked to arene core via ether or ester linkage. Lett. Drug Des. Discov., 2018, 15(10), 1036-1045.
[15]
Al Bogami, A.S.; Mekky, A.E.M. Microwave assisted regioselective synthesis of novel bis (azoles) and bis(azoloazines). J. Heterocyclic. Chem., 2016, 53, 1554-1562.
[16]
Sayed, O.M.; Mekky, A.E.M.; Farag, A.M.; Elwahy, A.H.M. 3,4 bis-(bromomethyl)thieno[2,3b]thiophene: Versatile precursors for novel bis(triazolothiadiazines), bis(quinoxalines), bis(dihydrooxadiazoles), and bis(dihydrothiadiazoles). J. Heterocycl. Chem., 2016, 53, 1113-1120.
[17]
Mekky, A.E.M.; Al-Bogami, A.S. Ultrasound assisted synthesis of some novel bis-pyridazine derivatives. J. Heterocycl. Chem., 2016, 53, 595-605.
[18]
Mehta, H.B.; Patel, P.K.; Dixit, B.C.; Dixit, R.B. Synthesis and antimicrobial activities of new mono and bisphenyl linked bispyrazole and bispyrazolone derivatives. Arab. J. Chem., 2017, 10, s1901-s1912.
[19]
Shawali, A.S. A review on bis-hydrazonoyl halides: Recent advances in their synthesis and their diverse synthetic applications leading to bis-heterocycles of biological interest. J. Adv. Res., 2016, 7, 873-907.
[20]
Murru, S.; Nefzi, A. Combinatorial synthesis of oxazol-thiazole bis-heterocyclic compounds. ACS Comb. Sci., 2014, 16, 39-45.
[21]
B’Bhatt. H.; Sharma, S. Synthesis and antimicrobial activity of pyrazole nucleus containing 2-thioxothiazolidin-4-one derivatives. Arab. J. Chem., 2017, 10, S1590-S1596.
[22]
Basha, S.S.; Divya, K.; Padmaja, A.; Padmavathi, V. Synthesis and antimicrobial activity of thiazolyl pyrazoles and isoxazoles synthesis and antimicrobial activity of thiazolyl pyrazoles and isoxazoles. Res. Chem. Intermediat., 2015, 41, 10067-10083.
[23]
Nagarapu, L.; Mateti, J.; Gaikwad, H.K.; Bantu, R.; Sheeba, R.M.; Prameela, S.N.J. Synthesis and anti-inflammatory activity of some novel 3-phenyl-N-[3-(4-phenylpiperazin-1yl) propyl]-1H-pyrazole-5-carboxamide derivatives. Bioorg. Med. Chem. Lett., 2011, 21, 4138-4140.
[24]
Alegaon, S.G.; Alagawadi, K.R.; Garg, M.K.; Dushyant, K.; Vinod, D. 1,3,4-Trisubstituted pyrazole analogues as promising anti-inflammatory agents. Bioorg. Chem., 2014, 54, 51-59.
[25]
Tewari, A.K.; Singh, V.P.; Yadav, P.; Gupta, G.; Singh, A.; Goel, R.K.; Shindae, P. Synthesis, biological evaluation and molecular modeling study of pyrazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Bioorg. Chem., 2014, 56, 8-15.
[26]
Reddy, T.S.; Kulhari, V.H.; Reddy, G.; Bansal, V.; Kamal, A.; Shukla, R. Design, synthesis and biological evaluation of 1,3-diphenyl-1H-pyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents. Eur. J. Med. Chem., 2015, 101, 790-805.
[27]
Xia, Y.; Dong, Z.W.; Zhao, B.X.; Ge, X.; Meng, N.; Shin, D.S.; Miao, J.Y. Synthesis and structure-activity relationships of novel 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide derivatives as potential agents against A549 lung cancer cells. Bioorg. Med. Chem., 2007, 15, 6893-6899.
[28]
Insuasty, B.; Tigreros, A.; Orozco, F.; Quiroga, J.; Abonía, R.; Nogueras, M.; Cobo, J. Synthesis of novel pyrazolic analogues of chalcones and their 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazole derivatives as potential antitumor agents. Bioorg. Med. Chem., 2010, 18, 4965-4974.
[29]
Regueiro-Ren, A.; Xue, Q.M.; Swidorski, J.J.; Gong, Y.F.; Mathew, M.; Parker, D.D.; Yang, Z.; Eggers, B.; D’Arienzo, C.; Sun, Y.; Malinowski, J.; Gao, Q.; Wu, D.; Langley, D.R.; Colonno, R.J.; Chien, C.; Grasela, D.M.; Zheng, M.; Lin, P.F.; Meanwell, N.A.; Kadow, J.F. Inhibitors of human immunodeficiency virus type 1 (HIV-1) attachment. 12. Structure-activity relationships associated with 4-fluoro-6-azaindole derivatives leading to the identification of 1-(4- benzoylpiperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1h-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dion. J. Med. Chem., 2013, 56, 1656-1669.
[30]
Fader, L.D.; Bethell, R.; Bonneau, P.; Bos, M.; Bousquet, Y.; Cordingley, M.G.; Coulombe, R.; Deroy, P.; Faucher, A.M.; Gagnon, A.; Goudreau, N.; GrandMaitre, C.; Guse, I.; Hucke, O.; Kawai, S.H.; Lacoste, J.E.; Landry, S.; Lemke, C.T.E.; Malenfant, S.; Mason, S.; Morin, J.; O’Meara, B.; Simoneau, S.; Titolo, C.; Yoakim, C. Discovery of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly. Bioorg. Med. Chem. Lett., 2011, 21, 398-404.
[31]
Nagamallu, R.; Srinivasan, B.; Ningappa, M.B.; Kariyappa, A.K. Synthesis of novel coumarin appended bis(formylpyrazole) derivatives: Studies on their antimicrobial and antioxidant activities. Bioorg. Med. Chem. Lett., 2016, 26(2), 690-694.
[32]
Prabhudeva, M.G.; Renuka, N.; Kumar, K.A. Synthesis of thiophene-pyrazole conjugates as potent antimicrobial and radical scavengers. Curr. Chem. Lett., 2018, 7, 73-80.
[33]
Renuka, N.; Vivek, H.K.; Pavithra, G.; Ajay, K. Synthesis of coumarin appended pyrazolyl-1,3,4-oxadiazoles and pyrazolyl-1,3,4-thiadiazoles: Evaluation of their in vitro antimicrobial and antioxidant activities and molecular docking studies. Russ. J. Bioorg Chem., 2017, 43, 197-210.
[34]
Whiteley, C.G. Arginine metabolising enzymes as targets against Alzheimer’s disease. Neurochem. Int., 2014, 67, 23-31.
[35]
Ewiss, N.F.; Osman, A. Synthesis of heterocycles. Part II. New routes to acetylthiadiazolines and alkylazothiazoles. J. Heterocycl. Chem., 1980, 17, 1713-1717.
[36]
Shawali, A.S.; Albar, H.A. Kinetics and mechanism of dehydrochlorination of N-aryl-C-ethoxycarbonylformohydrazidoyl chlorides. Cancer. J. Chem., 1986, 64, 871-875.
[37]
Cruickshank, R.; Duguid, J.P.; Marion, B.P.; Swain, R.H.A. Medicinal Microbiology, twelfth ed.; vol. II, Churchill Livingstone: London, 1975, pp. 196-202.
[38]
El-Gaby, M.S.A.; Hussein, A.M.; Abu-Shanab, F.A.; Desoky, H.M. Novel synthesis of pyrazole, bispyrazole and 2-pyridinone derivatives via cyanoacetohydrazides. Trends Heterocycl. Chem., 2008, 13, 79-84.
[39]
Toraskar, M.P.; Kamble, P.P. Enoyl acyl carrier protein reductase inhibitors: An emerging target. Int. J. Chemtech Res., 2018, 11, 123-133.
[40]
Tripathi, S.K.; Muttineni, R.; Singh, S.K. Extra precision docking, free energy calculation and molecular dynamics simulation studies of CDK2 inhibitors. J. Theoretical. Biol., 2013, 334, 87-100.
[41]
Molecular Operating Environment (MOE), Chemical Computing Group Inc., 1010 Sherbrooke Street West, Suite 910, Montréal, H3A 2R7, Canada, 2014. http://www.chemcomp.com