Login Register Cart 0
Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

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

Synthesis and Antibacterial / Anticancer Activities of Compounds Containing Pyrazole Ring Linked to Piperazines

Author(s): Kishore K. Valluri, Tejeswara R. Allaka, IV Kasi Viswanath* and Nagaraju PVVS

Volume 16, Issue 4, 2020

Page: [419 - 431] Pages: 13

DOI: 10.2174/1573407215666190111124513

Price: $65

Abstract

Background: Many pyrazole piperazine derivatives are known to exhibit a wide range, thus being attractive for the drug design and synthesis of interesting class of widely studied heterocyclic compounds. It is therefore necessary to devote continuing effort for the identification and development of New Chemical Entities (NCEs) as potential antibacterial and anticancer agents to address serious health problems.

Methods: A series of new compounds containing pyrazole ring linked to a piperazine hydrochloride moiety were synthesized and screened for their antibacterial activity, cytotoxicity of novel scaffolds are described by variation in therapeutic effects of parent molecule. The structure variants were characterized by using a blend of spectroscopic 1H NMR, 13C NMR, IR, Mass and chromatographic techniques.

Results: When tested for in vitro antibacterial and anticancer activities, several of these compounds showed good activities. The target compounds 9b, 9a and 9e exhibited a high degree of anticancer activity against human colon cancer cell line Caco-2 and human breast cancer cell line MDAMB231. Further, 9a, 9b, 9d, and 9h showed better activity towards four medically relevant organisms; Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Klebsiella Species compared to CPF. In the present investigation, cheminfomatics tools Molinspiration, 2003 and MolSoft, 2007 for the prediction of insilico molecular properties and drug likeness for the target compounds 9a-h was evaluated and positive results were observed.

Conclusion: Our study revealed that the molecular framework presented here could be a useful template for the identification of novel small molecules as promising antibacterial/ anticancer agents.

Keywords: Antibacterial activity, anticancer activity, pyrazole, Molinspiration, MolSoft, XRD studies.

Graphical Abstract

[1]
Detchokul, S.; Williams, E.D.; Parker, M.W.; Frauman, A.G. Tetraspanins as regulators of the tumour microenvironment: Implications for metastasis and therapeutic strategies. Br. J. Pharmacol., 2014, 171(24), 5462-5490.
[http://dx.doi.org/10.1111/bph.12260] [PMID: 23731188]
[2]
Hu, W. Hsin-Su Yu.; Yan-Ren chen.; Yi-Min Tsai.; Yin-kai Chen.; Chao-Cheng Liao.; Long-Sen Chang.; Jeh-Jeng Wang. Synthesis and biological evaluation of thio benzanilides as anticancer agents. Bioorg. Med. Chem., 2008, 16, 5295-5302.
[http://dx.doi.org/10.1016/j.bmc.2008.03.003] [PMID: 18359635]
[3]
Kemnitzer, W.; Jiang, S.; Wang, Y.; Kasibhatla, S.; Crogan-Grundy, C.; Bubenik, M.; Labrecque, D.; Denis, R.; Lamothe, S.; Attardo, G.; Gourdeau, H.; Tseng, B.; Drewe, J.; Cai, S.X. Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based HTS assay. Part 5: Modifications of the 2- and 3-positions. Bioorg. Med. Chem. Lett., 2008, 18(2), 603-607.
[http://dx.doi.org/10.1016/j.bmcl.2007.11.078] [PMID: 18077161]
[4]
Bondock, S.; Khalifa, W.; Fadda, A.A. Synthesis and antimicrobial activity of some new 4-hetarylpyrazole and furo[2,3-c]pyrazole derivatives. Eur. J. Med. Chem., 2011, 46(6), 2555-2561.
[http://dx.doi.org/10.1016/j.ejmech.2011.03.045] [PMID: 21489661]
[5]
Sanjeeva Reddy, C.; Sanjeeva Rao, L.; Rajesh Kumar, G.; Nagaraj, A. Synthesis of new 1,2,4-triazole[3,4-b][1,3,4]thiadiazoles bearing pyrazole as potent antimicrobial agents. Chem. Pharm. Bull. (Tokyo), 2010, 58(10), 1328-1331.
[http://dx.doi.org/10.1248/cpb.58.1328] [PMID: 20930399]
[6]
Patel, M.V.; Bell, R.; Majest, S.; Henry, R.; Kolasa, T. Synthesis of 4,5-diaryl-1H-pyrazole-3-ol derivatives as potential COX-2 inhibitors. J. Org. Chem., 2004, 69(21), 7058-7065.
[http://dx.doi.org/10.1021/jo049264k] [PMID: 15471453]
[7]
Bansode, T.N.; Shelke, J.V.; Dongre, V.G. Synthesis and antimicrobial activity of some new N-acyl substituted phenothiazines. Eur. J. Med. Chem., 2009, 44(12), 5094-5098.
[http://dx.doi.org/10.1016/j.ejmech.2009.07.006] [PMID: 19651462]
[8]
Santos, J.L.; Yamasaki, P.R.; Chin, C.M.; Takashi, C.H.; Pavan, F.R.; Leite, C.Q. Synthesis and in vitro anti Mycobacterium tuberculosis activity of a series of phthalimide derivatives. Bioorg. Med. Chem., 2009, 17(11), 3795-3799.
[http://dx.doi.org/10.1016/j.bmc.2009.04.042] [PMID: 19427791]
[9]
Christodoulou, M.S.; Liekens, S.; Kasiotis, K.M.; Haroutounian, S.A. Novel pyrazole derivatives: Synthesis and evaluation of anti-angiogenic activity. Bioorg. Med. Chem., 2010, 18(12), 4338-4350.
[http://dx.doi.org/10.1016/j.bmc.2010.04.076] [PMID: 20493716]
[10]
Ragavan, R.V.; Vijayakumar, V.; Kumari, N.S. Synthesis and antimicrobial activities of novel 1,5-diaryl pyrazoles. Eur. J. Med. Chem., 2010, 45(3), 1173-1180.
[http://dx.doi.org/10.1016/j.ejmech.2009.12.042] [PMID: 20053480]
[11]
Rangaswamy, J.; Kumar, H.V.; Harini, S.T.; Naik, N. Synthesis of benzofuran based 1,3,5-substituted pyrazole derivatives: as a new class of potent antioxidants and antimicrobials-A novel accost to amend biocompatibility. Bioorg. Med. Chem. Lett., 2012, 22(14), 4773-4777.
[http://dx.doi.org/10.1016/j.bmcl.2012.05.061] [PMID: 22695127]
[12]
Zhang, C.Y.; Liu, X.H.; Wang, B.L.; Wang, S.H.; Li, Z.M. Synthesis and antifungal activities of new pyrazole derivatives via 1,3-dipolar cycloaddition reaction. Chem. Biol. Drug Des., 2010, 75(5), 489-493.
[http://dx.doi.org/10.1111/j.1747-0285.2010.00948.x] [PMID: 20486935]
[13]
El-Sayed Ali, T. Synthesis of some novel pyrazolo[3,4-b]pyridine and pyrazolo[3,4-d]pyrimidine derivatives bearing 5,6-diphenyl-1,2,4-triazine moiety as potential antimicrobial agents. Eur. J. Med. Chem., 2009, 44(11), 4385-4392.
[http://dx.doi.org/10.1016/j.ejmech.2009.05.031] [PMID: 19586688]
[14]
Xie, L.; Cui, J.; Qian, X.; Xu, Y.; Liu, J.; Xu, R. 5-Non-amino aromatic substituted naphthalimides as potential antitumor agents: Synthesis via Suzuki reaction, antiproliferative activity, and DNA-binding behavior. Bioorg. Med. Chem., 2011, 19(2), 961-967.
[http://dx.doi.org/10.1016/j.bmc.2010.11.055] [PMID: 21208805]
[15]
Riyadh, S.M.; Farghaly, T.A.; Abdallah, M.A.; Abdalla, M.M.; Abd El-Aziz, M.R. New pyrazoles incorporating pyrazolylpyrazole moiety: synthesis, anti-HCV and antitumor activity. Eur. J. Med. Chem., 2010, 45(3), 1042-1050.
[http://dx.doi.org/10.1016/j.ejmech.2009.11.050] [PMID: 20022411]
[16]
Hashimoto, H.; Imamura, K.; Haruta, J.; Wakitani, K. 4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as selective cyclooxygenase-2 inhibitors: enhancement of the selectivity by introduction of a fluorine atom and identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522(1). J. Med. Chem., 2002, 45(7), 1511-1517.
[http://dx.doi.org/10.1021/jm010484p] [PMID: 11906292]
[17]
Ranatunge, R.R.; Earl, R.A.; Garvey, D.S.; Janero, D.R.; Letts, L.G.; Martino, A.M.; Murty, M.G.; Richardson, S.K.; Schwalb, D.J.; Young, D.V.; Zemtseva, I.S. 3-(2-Methoxytetrahydrofuran-2-yl)pyrazoles: a novel class of potent, selective Cyclooxygenase-2 (COX-2) inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(24), 6049-6052.
[http://dx.doi.org/10.1016/j.bmcl.2004.09.073] [PMID: 15546727]
[18]
Li, Y.L.; Fevig, J.M.; Cacciola, J.; Buriak, J., Jr; Rossi, K.A.; Jona, J.; Knabb, R.M.; Luettgen, J.M.; Wong, P.C.; Bai, S.A.; Wexler, R.R.; Lam, P.Y.S. Preparation of 1-(3-aminobenzo[d]isoxazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones as potent, selective, and efficacious inhibitors of coagulation factor Xa. Bioorg. Med. Chem. Lett., 2006, 16(19), 5176-5182.
[http://dx.doi.org/10.1016/j.bmcl.2006.07.002] [PMID: 16870435]
[19]
Fevig, J.M.; Cacciola, J.; Buriak, J., Jr; Rossi, K.A.; Knabb, R.M.; Luettgen, J.M.; Wong, P.C.; Bai, S.A.; Wexler, R.R.; Lam, P.Y.S. Preparation of 1-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones as potent, selective and bioavailable inhibitors of coagulation factor Xa. Bioorg. Med. Chem. Lett., 2006, 16(14), 3755-3760.
[http://dx.doi.org/10.1016/j.bmcl.2006.04.044] [PMID: 16682200]
[20]
Pinto, D.J.P.; Orwat, M.J.; Koch, S.; Rossi, K.A.; Alexander, R.S.; Smallwood, A.; Wong, P.C.; Rendina, A.R.; Luettgen, J.M.; Knabb, R.M.; He, K.; Xin, B.; Wexler, R.R.; Lam, P.Y.S. Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa. J. Med. Chem., 2007, 50(22), 5339-5356.
[http://dx.doi.org/10.1021/jm070245n] [PMID: 17914785]
[21]
Chou, L.C.; Huang, L.J.; Yang, J.S.; Lee, F.Y.; Teng, C.M.; Kuo, S.C. Synthesis of furopyrazole analogs of 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) as novel anti-leukemia agents. Bioorg. Med. Chem., 2007, 15(4), 1732-1740.
[http://dx.doi.org/10.1016/j.bmc.2006.12.001] [PMID: 17189698]
[22]
Knorr, L. Chem. Ber., 1883, 17, 546-555.
[http://dx.doi.org/10.1002/cber.188401701152]
[23]
Wei, F.; Zhao, B.X.; Dong, W.L.; Zuo, H.; Shin, D.S.; Wang, D.W.; Xia, Y.; Ge, Y.Q. Microwave‐assisted rapid and straightforward synthesis of novel 6‐(Aroxymethyl)‐2 ‐aryl‐6,7‐dihydropyrazolo[5,1‐c][1,4]oxazin‐4‐one derivatives. Synth. Commun., 2007, 37, 4415-4424.
[http://dx.doi.org/10.1080/00397910701577877]
[24]
Xie, Y.S.; Zhao, B.X.; Lv, H.S.; Li, J.K.; Wang, B.S.; Shin, D.S. Synthesis and single-crystal characterization of novel 2-ferrocenyl-4H-pyrazolo[5,1-c][1,4]oxazin-4-one derivatives. J. Mol. Struct., 2009, 930, 83-87.
[http://dx.doi.org/10.1016/j.molstruc.2009.04.042]
[25]
Xie, Y.S.; Zhao, H.L.; Su, H.; Zhao, B.X.; Liu, J.T.; Li, J.K.; Lv, H.S.; Wang, B.S.; Shin, D.S.; Miao, J.Y. Synthesis, single-crystal characterization and preliminary biological evaluation of novel ferrocenyl pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives. Eur. J. Med. Chem., 2010, 45(1), 210-218.
[http://dx.doi.org/10.1016/j.ejmech.2009.09.046] [PMID: 19879668]
[26]
Zhang, J.H.; Fan, C.D.; Zhao, B.X.; Shin, D.S.; Dong, W.L.; Xie, Y.S.; Miao, J.Y. Synthesis and preliminary biological evaluation of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as potential agents against A549 lung cancer cells. Bioorg. Med. Chem., 2008, 16(24), 10165-10171.
[http://dx.doi.org/10.1016/j.bmc.2008.10.066] [PMID: 19013820]
[27]
Xie, Y.S.; Pan, X.H.; Zhao, B.X.; Liu, J.T.; Shin, D.S.; Zhang, J.H.; Zheng, L.W.; Zhao, J.; Miao, J.Y. Synthesis, structure characterization and preliminary biological evaluation of novel 5-alkyl-2-ferrocenyl-6,7-dihydropyrazolo[1,5-a]pyrazin-4-(5H)-one derivatives. J. Organomet. Chem., 2008, 693, 1367-1374.
[http://dx.doi.org/10.1016/j.jorganchem.2008.01.043]
[28]
Tewari, A.K.; Srivastava, P.; Singh, V.P.; Singh, A.; Goel, R.K.; Mohan, C.G. Novel anti-inflammatory agents based on pyrazole based dimeric compounds; design, synthesis, docking and in vivo activity. Chem. Pharm. Bull. (Tokyo), 2010, 58(5), 634-638.
[http://dx.doi.org/10.1248/cpb.58.634] [PMID: 20460788]
[29]
MolSoft. http://www.molinspiration.com 2007.
[30]
Bakht, M.A.; Yar, M.S.; Abdel-Hamid, S.G.; Al Qasoumi, S.I.; Samad, A. Molecular properties prediction, synthesis and antimicrobial activity of some newer oxadiazole derivatives. Eur. J. Med. Chem., 2010, 45(12), 5862-5869.
[http://dx.doi.org/10.1016/j.ejmech.2010.07.069] [PMID: 20965619]
[31]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[32]
Rajanarendar, E.; Rama Krishna, S.; Nagaraju, D.; Govardhan Reddy, K.; Kishore, B.; Reddy, Y.N. Environmentally benign synthesis, molecular properties prediction and anti-inflammatory activity of novel isoxazolo[5,4-d]isoxazol-3-yl-aryl-methanones via vinylogous Henry nitroaldol adducts as synthons. Bioorg. Med. Chem. Lett., 2015, 25(7), 1630-1634.
[http://dx.doi.org/10.1016/j.bmcl.2015.01.041] [PMID: 25708616]
[33]
Ertl, P.; Rohde, B.; Selzer, P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J. Med. Chem., 2000, 43(20), 3714-3717.
[http://dx.doi.org/10.1021/jm000942e] [PMID: 11020286]
[34]
Alafeefy, A.M.; Alqasoumi, S.I.; Ashour, A.E.; Masand, V.; Al-Jaber, N.A.; Ben Hadda, T.; Mohamed, M.A. Quinazoline-tyrphostin as a new class of antitumor agents, molecular properties prediction, synthesis and biological testing. Eur. J. Med. Chem., 2012, 53, 133-140.
[http://dx.doi.org/10.1016/j.ejmech.2012.03.044] [PMID: 22520152]
[35]
da Silva, M.M.; Comin, M.; Duarte, T.S.; Foglio, M.A.; de Carvalho, J.E.; do Vieira, M.C.; Formagio, A.S. Synthesis, antiproliferative activity and molecular properties predictions of galloyl derivatives. Molecules, 2015, 20(4), 5360-5373.
[http://dx.doi.org/10.3390/molecules20045360] [PMID: 25816079]
[36]
Kavanagh, F. Analytical Microbiology; Academic Press: New York, London, 1972, Vol. II, pp. 11-23.
[37]
Miles, A.A.; Misra, S.S.; Irwin, J.O. The estimation of the bactericidal power of the blood. J. Hyg. (Lond.), 1938, 38(6), 732-749.
[PMID: 20475467]
[38]
Botta, M.; Armaroli, S.; Castagnolo, D.; Fontana, G.; Pera, P.; Bombardelli, E. Synthesis and biological evaluation of new taxoids derived from 2-deacetoxytaxinine J. Bioorg. Med. Chem. Lett., 2007, 17(6), 1579-1583.
[http://dx.doi.org/10.1016/j.bmcl.2006.12.101] [PMID: 17254787]

Rights & Permissions Print Cite
Article Metrics
6
1
© 2024 Bentham Science Publishers | Privacy Policy