Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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

Synthesis, Antimicrobial, Antioxidant and Molecular Docking Studies on Novel 6-Methoxybenzothiazole-piperazine Derivatives with Propanamide Chain

Author(s): Nesrin Atiah Alhusadi, Bengisu Turgutalp, Inci Deniz, Ebru Turkoz Acar, Hande Sipahi*, Mine Yarim and Enise Ece Gurdal*

Volume 20, Issue 19, 2020

Page: [1733 - 1741] Pages: 9

DOI: 10.2174/1568026620666200618122500

Price: $65

Abstract

Background: Infectious diseases are a major threat in the developing world and the discovery of novel antimicrobial agents remains to be crucial due to acquired resistance by the microorganisms. Additionally, various diseases can be prevented with antioxidant agents as they can eliminate the harmful effects of reactive oxygen species.

Objective: In this study, it was aimed to synthesize novel compounds bearing N-(6- methoxybenzothiazol-2-yl)-3-(4-substitued piperazinyl)propanamide backbone that had antimicrobial and antioxidant activities. Mechanisms of activity were aimed to be revealed by docking studies.

Methods: Antimicrobial activities were tested by agar-based disc diffusion assay, and antioxidant activities were determined by CUPRAC assay.

Results: In agar-based disc diffusion assay, the most active compounds were 2b and 2e against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. Compounds 2e and 2j showed promising antioxidant activity in CUPRAC assay. Docking studies were performed to optimize the interactions of compounds with DNA gyrase subunit B of S. aureus. Under the light of docking studies, a new compound with potential GyrB inhibition was designed. Antioxidant activity was also supported by docking studies on superoxide dismutase 1 enzyme in which interactions with key residues were observed.

Conclusion: Ten novel benzothiazole-piperazine derivatives were synthesized and their antimicrobial and antioxidant activities were evaluated. Superoxide dismutase 1 enzyme was suggested to be a possible target for the antioxidant activity of the series.

Keywords: Antibacterial, Antifungal, Antioxidant, Benzothiazole, Docking, Piperazine.

« Previous Next »
Graphical Abstract

[1]
Gajdács, M. The concept of an ideal antibiotic: Implications for drug design. Molecules, 2019, 24(5), 892.
[http://dx.doi.org/10.3390/molecules24050892] [PMID: 30832456]
[2]
Sindhia, V.; Guptaa, V.; Sharmaa, K.; Bhatnagarb, S.; Kumaria, R.; Dhaka, N. Potential applications of antioxidants – A review. J. Pharm. Res., 2013, 7(9), 828-835.
[http://dx.doi.org/10.1016/j.jopr.2013.10.001]
[3]
Demir Özkay, Ü.; Kaya, C.; Acar Çevik, U.; Can, Ö.D. Synthesis and antidepressant activity profile of some novel benzothiazole derivatives. Molecules, 2017, 22(9), 1490.
[http://dx.doi.org/10.3390/molecules22091490] [PMID: 28880242]
[4]
Chen, L.; Chen, H.; Chen, P.; Zhang, W.; Wu, C.; Sun, C.; Luo, W.; Zheng, L.; Liu, Z.; Liang, G. Development of 2-amino-4-phenylthiazole analogues to disrupt myeloid differentiation factor 88 and prevent inflammatory responses in acute lung injury. Eur. J. Med. Chem., 2019, 161, 22-38.
[http://dx.doi.org/10.1016/j.ejmech.2018.09.068] [PMID: 30342423]
[5]
Raghavendra, N.M.; Jyothsna, A.; Venkateswara Rao, A.; Subrahmanyam, C.V.S. Synthesis, pharmacological evaluation and docking studies of N-(benzo[d]thiazol-2-yl)-2-(piperazin-1-yl)acetamide analogs as COX-2 inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(2), 820-823.
[http://dx.doi.org/10.1016/j.bmcl.2011.12.062] [PMID: 22222039]
[6]
Al-Soud, Y.A.; Al-Sa’doni, H.H.; Saeed, B.; Jaber, I.H.; Beni-Khalid, M.O.; Al-Masoudi, N.A.; Abdul-Kadir, T.; La Colla, P.; Busonera, B.; Sanna, T.; Loddo, R. Synthesis and in vitro antiproliferative activity of new benzothiazole derivatives. ARKIVOC, 2008, 15, 225-238.
[7]
Demir Özkay, Ü.; Can, Ö.D.; Sağlık, B.N.; Acar Çevik, U.; Levent, S.; Özkay, Y.; Ilgın, S.; Atlı, Ö. Design, synthesis, and AChE inhibitory activity of new benzothiazole-piperazines. Bioorg. Med. Chem. Lett., 2016, 26(22), 5387-5394.
[http://dx.doi.org/10.1016/j.bmcl.2016.10.041] [PMID: 27789142]
[8]
Gurdal, E.E.; Turgutalp, B.; Gulcan, H.O.; Ercetin, T.; Sahin, M.F.; Durmaz, I.; Atalay, R.C.; Nguyen, Q.D.; Sippl, W.; Yarim, M. Synthesis of novel benzothiazole-piperazine derivatives and their biological evaluation as acetylcholinesterase inhibitors and cytotoxic agents. Anticancer. Agents Med. Chem., 2017, 17(13), 1837-1845.
[PMID: 28403780]
[9]
Sharma, P.C.; Kumar, R.; Chaudhary, M.; Sharma, A.; Rajak, H. Synthesis and biological evaluation of novel benzothiazole clubbed fluoroquinolone derivatives. J. Enzyme Inhib. Med. Chem., 2013, 28(1), 1-10.
[http://dx.doi.org/10.3109/14756366.2011.611943] [PMID: 21981002]
[10]
Kładna, A.; Berczyński, P.; Dündar, O.B.; Ünlüsoy, M.C.; Sarı, E.; Bakinowska, B.; Kruk, I.; Aboul-Enein, H.Y. Synthesis and in vitro antioxidant activity of new pyrimidin/benzothiazol-substituted piperazinyl flavones. Future Med. Chem., 2018, 10(19), 2293-2308.
[http://dx.doi.org/10.4155/fmc-2018-0206] [PMID: 30273015]
[11]
Papadopoulou, C.; Geronikaki, A.; Hadjipavlou-Litina, D. Synthesis and biological evaluation of new thiazolyl/benzothiazolyl-amides, derivatives of 4-phenyl-piperazine. Farmaco, 2005, 60(11-12), 969-973.
[http://dx.doi.org/10.1016/j.farmac.2005.06.014] [PMID: 16040029]
[12]
Balkan, İ.A.; Taşkın, T.; Doğan, H.T.; Deniz, İ.; Akaydın, G.; Yesilada, E. A comparative investigation on the in vitro anti-inflammatory, antioxidant and antimicrobial potentials of subextracts from the aerial parts of Daphne oleoides Schreb. subsp. oleoides. Ind. Crops Prod., 2017, 95, 695-703.
[http://dx.doi.org/10.1016/j.indcrop.2016.11.038]
[13]
Güçlü, K.; Sözgen, K.; Tütem, E.; Ozyürek, M.; Apak, R. Spectrophotometric determination of ascorbic acid using copper(II)-neocuproine reagent in beverages and pharmaceuticals. Talanta, 2005, 65(5), 1226-1232.
[http://dx.doi.org/10.1016/j.talanta.2004.08.048] [PMID: 18969936]
[14]
Friesner, R.A.; Murphy, R.B.; Repasky, M.P.; Frye, L.L.; Greenwood, J.R.; Halgren, T.A.; Sanschagrin, P.C.; Mainz, D.T. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem., 2006, 49(21), 6177-6196.
[http://dx.doi.org/10.1021/jm051256o] [PMID: 17034125]
[15]
Watts, K.S.; Dalal, P.; Murphy, R.B.; Sherman, W.; Friesner, R.A.; Shelley, J.C. ConfGen: a conformational search method for efficient generation of bioactive conformers. J. Chem. Inf. Model., 2010, 50(4), 534-546.
[http://dx.doi.org/10.1021/ci100015j] [PMID: 20373803]
[16]
Schwab, C.H. Conformations and 3D pharmacophore searching. Drug Discov. Today. Technol., 2010, 7(4), e203-e270.
[http://dx.doi.org/10.1016/j.ddtec.2010.10.003] [PMID: 24103800]
[17]
Duan, J.; Dixon, S.L.; Lowrie, J.F.; Sherman, W. Analysis and comparison of 2D fingerprints: insights into database screening performance using eight fingerprint methods. J. Mol. Graph. Model., 2010, 29(2), 157-170.
[http://dx.doi.org/10.1016/j.jmgm.2010.05.008] [PMID: 20579912]
[18]
Eakin, A.E.; Green, O.; Hales, N.; Walkup, G.K.; Bist, S.; Singh, A.; Mullen, G.; Bryant, J.; Embrey, K.; Gao, N.; Breeze, A.; Timms, D.; Andrews, B.; Uria-Nickelsen, M.; Demeritt, J.; Loch, J.T., III; Hull, K.; Blodgett, A.; Illingworth, R.N.; Prince, B.; Boriack-Sjodin, P.A.; Hauck, S.; MacPherson, L.J.; Ni, H.; Sherer, B. Pyrrolamide DNA gyrase inhibitors: fragment-based nuclear magnetic resonance screening to identify antibacterial agents. Antimicrob. Agents Chemother., 2012, 56(3), 1240-1246.
[http://dx.doi.org/10.1128/AAC.05485-11] [PMID: 22183167]
[19]
Kershaw, N.M.; Wright, G.S.; Sharma, R.; Antonyuk, S.V.; Strange, R.W.; Berry, N.G.; O’Neill, P.M.; Hasnain, S.S. X-ray crystallography and computational docking for the detection and development of protein-ligand interactions. Curr. Med. Chem., 2013, 20(4), 569-575.
[PMID: 23278398]
[20]
Schrödinger Release In: QikProp; Schrödinger, LLC: New York, NY, 2019.

Rights & Permissions Print Cite
Article Metrics
14
2
© 2024 Bentham Science Publishers | Privacy Policy