Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Synthesis, Antiproliferative, and Antioxidant Activities of Substituted N-[(1,3,4-Oxadiazol-2-yl) Methyl] Benzamines

Author(s): Mohamed Jawed Ahsan*, Lakshya Bhandari, Shally Makkar, Rajan Singh, Mohd. Zaheen Hassan, Mohammed H. Geesi, Mohamed Afroz Bakht, Surender Singh Jadav, Tuniki Balaraju, Yassine Riadi , Sandhya Rani, Habibullah Khalilullah, Vasubabu Gorantla and Afzal Hussain

Volume 17, Issue 2, 2020

Page: [145 - 154] Pages: 10

DOI: 10.2174/1570180816666181113110033

Price: $65

Abstract

Background: Oxadiazole emerged as an important class of heterocyclic compound with diverse biological activities like anticancer, antitubercular, anticonvulsant, anti-tubulin, antimicrobial, anti-inflammatory, antioxidant etc.

Objective: The objective of this study is to synthesis series of twelve substituted N-[(1,3,4-oxadiazol-2- yl)methyl]benzamines (6a-l) and their evaluation as antiproliferative and antioxidant agents.

Methods: The substituted N-[(1,3,4-oxadiazol-2-yl)methyl]benzamines (6a-l) analogues were synthesized as per the reported procedure. The antiproliferative activity was tested against nine different panels cancer cell lines (leukemia, colon, renal, non-small cell lung, breast, CNS, melanoma, prostate, and ovarian cancer) at 10 µM drug concentrations as per the NCI US Protocol.

Results: 2-(5-((3-Chloro-4-fluorophenylamino)methyl)-1,3,4-oxadiazol-2-yl)phenol (6e) revealed the significant antiproliferative activity among the series of title compounds (6a-l). The compound, 6e showed maximum sensitivity towards CCRF-CEM, MCF-7, MOLT-4, T-47D, and SR cell lines with percent growth inhibitions (%GIs) of 79.92, 56.67, 39.62, 34.71 and 33.35, respectively. Furthermore, the compounds, 6e and 6c showed promising antioxidant activity with an IC50 value of 15.09 and 19.02 µM, respectively in DPPH free radicals (FR) scavenging activity.

Conclusion: The present study may support a significant value in cancer drug discovery programme.

Keywords: Anti-proliferative agents, antioxidants, oxadiazoles, one dose assay, DPPH, free radicals scavenging activity.

Graphical Abstract

[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin., 2018, 68(1), 7-30.
[http://dx.doi.org/10.3322/caac.21442] [PMID: 29313949]
[2]
Aydemir, N.; Bilaloğlu, R. Genotoxicity of two anticancer drugs, gemcitabine and topotecan, in mouse bone marrow in vivo. Mutat. Res., 2003, 537(1), 43-51.
[http://dx.doi.org/10.1016/S1383-5718(03)00049-4] [PMID: 12742506]
[3]
Vaidya, A.; Jain, S.; Jain, P.; Jain, P.; Tiwari, N.; Jain, R.; Jain, R.; Jain, A.K.; Agrawal, R.K. Synthesis and Biological Activities of Oxadiazole Derivatives: A Review. Mini Rev. Med. Chem., 2016, 16(10), 825-845.
[http://dx.doi.org/10.2174/1389557516666160211120835] [PMID: 26864552]
[4]
Zhang, K.; Wang, P.; Xuan, L.N.; Fu, X.Y.; Jing, F.; Li, S.; Liu, Y.M.; Chen, B.Q. Synthesis and antitumor activities of novel hybrid molecules containing 1,3,4-oxadiazole and 1,3,4-thiadiazole bearing Schiff base moiety. Bioorg. Med. Chem. Lett., 2014, 24(22), 5154-5156.
[http://dx.doi.org/10.1016/j.bmcl.2014.09.086] [PMID: 25442303]
[5]
Kamal, A.; Srikanth, P.S.; Vishnuvardhan, M.V.P.S.; Kumar, G.B.; Suresh Babu, K.; Hussaini, S.M.A.; Kapure, J.S.; Alarifi, A. Combretastatin linked 1,3,4-oxadiazole conjugates as a Potent Tubulin Polymerization inhibitors. Bioorg. Chem., 2016, 65, 126-136.
[http://dx.doi.org/10.1016/j.bioorg.2016.02.007] [PMID: 26943479]
[6]
Ahsan, M.J.; Choupra, A.; Sharma, R.K.; Jadav, S.S.; Padmaja, P.; Hassan, M.Z.; Al-Tamimi, A.B.S.; Geesi, M.H.; Bakht, M.A. Rationale design, synthesis, cytotoxicity evaluation, and molecular docking studies of 1,3,4-oxadiazole analogues. Anticancer. Agents Med. Chem., 2018, 18(1), 121-138.
[http://dx.doi.org/10.2174/1871520617666170419124702] [PMID: 28425854]
[7]
Shingare, R.M.; Patil, Y.S.; Sangshetti, J.N.; Patil, R.B.; Rajani, D.P.; Madje, B.R. Synthesis, biological evaluation and docking study of some novel isoxazole clubbed 1,3,4-oxadiazoles derivatives. Med. Chem. Res., 2018, 27, 1283-1291.
[http://dx.doi.org/10.1007/s00044-018-2148-2]
[8]
Khan, M.H.; Hameed, S.; Akhtar, T.; Al-Masoudi, W.A.; Jones, P.G.; Pannecouque, C. Synthesis, crystal structure, and molecular docking study of new thiazdiazole and thiazole analogues as potential anti-HIV agents. Med. Chem. Res., 2016, 25, 2399-2409.
[http://dx.doi.org/10.1007/s00044-016-1669-9]
[9]
Khan, M.U.; Akhtar, T.; Al-Masoudi, N.A.; Stoeckli-Evans, H.; Hameed, S. Synthesis, crystal structure and anti-HIV activity of 2-adamantyl/adamantylmethyl-5-aryl-1,3,4-oxadiazoles. Med. Chem., 2012, 8(6), 1190-1197.
[PMID: 22741800]
[10]
Ouyang, X.; Piatnitski, E.L.; Pattaropong, V.; Chen, X.; He, H.Y.; Kiselyov, A.S.; Velankar, A.; Kawakami, J.; Labelle, M.; Smith, LII.; Lohman, J.; Lee, S.P.; Malikzay, A.; Fleming, J.; Gerlak, J.; Wang, Y.; Rosler, R.L.; Zhou, K.; Mitelman, S.; Camara, M.; Surguladze, D.; Doody, J.F.; Tuma, M.C. Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines. Bioorg. Med. Chem. Lett., 2006, 16(5), 1191-1196.
[http://dx.doi.org/10.1016/j.bmcl.2005.11.094] [PMID: 16377187]
[11]
Ahsan, M.J.; Samy, J.G.; Khalilullah, H.; Nomani, M.S.; Saraswat, P.; Gaur, R.; Singh, A. Molecular properties prediction and synthesis of novel 1,3,4-oxadiazole analogues as potent antimicrobial and antitubercular agents. Bioorg. Med. Chem. Lett., 2011, 21(24), 7246-7250.
[http://dx.doi.org/10.1016/j.bmcl.2011.10.057] [PMID: 22071303]
[12]
Rathore, A.; Sudhakar, R.; Ahsan, M.J.; Ali, A.; Subbarao, N.; Jadav, S.S.; Umar, S.; Yar, M.S. In vivo anti-inflammatory activity and docking study of newly synthesized benzimidazole derivatives bearing oxadiazole and morpholine rings. Bioorg. Chem., 2017, 70, 107-117.
[http://dx.doi.org/10.1016/j.bioorg.2016.11.014] [PMID: 27923497]
[13]
Sahoo, B.M.; Dinda, S.C. RaviKumar, B.V.V.; Panda, J.; Brahmkshatriya, P.S. Design, Green Synthesis, and Anti-Inflammatory Activity of Schiff Base of 1,3,4-oxadiazole Analogues. Lett. Drug Des. Discov., 2014, 11, 82-89.
[http://dx.doi.org/10.2174/15701808113109990041]
[14]
Tabatabai, S.A.; Barghi Lashkari, S.; Zarrindast, M.R.; Gholibeikian, M.; Shafiee, A. Design, Synthesis and Anticonvulsant Activity of 2-(2-Phenoxy) phenyl- 1,3,4-oxadiazole Derivatives. Iran. J. Pharm. Res., 2013, 12(Suppl.), 105-111.
[PMID: 24250678]
[15]
Ahsan, M.J.; Meena, R.; Dubey, S.; Khan, V.; Manda, S.; Jadav, S.S.; Sharma, P. Geesi, M.H.; Hassan, M.Z.; Bakht, M.A.; Riadi, Y.; Akhter, M.H.; Salahuddin.; Gundla, R. Synthesis and biological potentials of some new oxadiazole analogues. Med. Chem. Res., 2018, 27, 864-883.
[16]
Birben, E.; Sahiner, U.M.; Sackesen, C.; Erzurum, S.; Kalayci, O. Oxidative stress and antioxidant defense. World Allergy Organ. J., 2012, 5(1), 9-19.
[http://dx.doi.org/10.1097/WOX.0b013e3182439613] [PMID: 23268465]
[17]
Reuter, S.; Gupta, S.C.; Chaturvedi, M.M.; Aggarwal, B.B. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic. Biol. Med., 2010, 49(11), 1603-1616.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.09.006] [PMID: 20840865]
[18]
Pham-Huy, L.A.; He, H.; Pham-Huy, C. Free radicals, antioxidants in disease and health. Int. J. Biomed. Sci., 2008, 4(2), 89-96.
[PMID: 23675073]
[19]
Ahsan, M.J.; Yadav, R.P.; Saini, S.; Hassan, M.Z.; Bakht, M.A.; Jadav, S.S.; Al-Tamimi, A.B.S.; Geesi, M.H.; Ansari, M.Y.; Habibullah, K.; Riadi, Y. Synthesis, cytotoxic evaluation, and molecular docking studies of new oxadiazole analogues. Lett. Org. Chem., 2018, 15, 49-56.
[20]
Yadav, D.K.; Dhawan, S.; Chauhan, A.; Qidwai, T.; Sharma, P.; Bhakuni, R.S.; Dhawan, O.P.; Khan, F. QSAR and docking based semi-synthesis and in vivo evaluation of artemisinin derivatives for antimalarial activity. Curr. Drug Targets, 2014, 15(8), 753-761.
[http://dx.doi.org/10.2174/1389450115666140630102711] [PMID: 24975562]
[21]
Yadav, D.K.; Kalani, K.; Singh, A.K.; Khan, F.; Srivastava, S.K.; Pant, A.B. Design, synthesis and in vitro evaluation of 18β-glycyrrhetinic acid derivatives for anticancer activity against human breast cancer cell line MCF-7. Curr. Med. Chem., 2014, 21(9), 1160-1170.
[http://dx.doi.org/10.2174/09298673113206660330] [PMID: 24180274]
[22]
Yadav, D.K.; Khan, F.; Negi, A.S. Pharmacophore modeling, molecular docking, QSAR, and in silico ADMET studies of gallic acid derivatives for immunomodulatory activity. J. Mol. Model., 2012, 18(6), 2513-2525.
[http://dx.doi.org/10.1007/s00894-011-1265-3] [PMID: 22038459]
[23]
Yadav, D.K.; Kalani, K.; Khan, F.; Srivastava, S.K. QSAR and docking based semi-synthesis and in vitro evaluation of 18 β-glycyrrhetinic acid derivatives against human lung cancer cell line A-549. Med. Chem., 2013, 9(8), 1073-1084.
[http://dx.doi.org/10.2174/1573406411309080009] [PMID: 23675978]
[24]
Yadav, D.K.; Khan, F. QSAR, docking and ADMET studies of camptothecin derivatives as inhibitors of DNA topoisomerase‐I. J. Chemometr., 2013, 27, 21-33.
[http://dx.doi.org/10.1002/cem.2488]
[25]
Yadav, D.K.; Kumar, S. Saloni; Singh, H.; Kim, M.H.; Sharma, P.; Misra, S.; Khan, F. Molecular docking, QSAR and ADMET studies of withanolide analogs against breast cancer. Drug Des. Devel. Ther., 2017, 11, 1859-1870.
[http://dx.doi.org/10.2147/DDDT.S130601] [PMID: 28694686]
[26]
Finger, G.C.; Dickerson, D.R.; Starr, L.D.; Orlopp, D.E. Aromatic fluorine compounds. XIII. Substituted N-phenylglycine ethyl esters and hydrazides. J. Med. Chem., 1965, 8, 405-407.
[http://dx.doi.org/10.1021/jm00327a036] [PMID: 14323166]
[27]
Bhat, M.A.; Al-Omar, M.A.; Ansari, M.A.; Zoheir, K.M.A.; Imam, F.; Attia, S.M.; Bakheet, S.A.; Nadeem, A.; Korashy, H.M.; Voronkov, A.; Berishvili, V.; Ahmad, S.F. Design and synthesis of N-arylphthalimides as inhibitors of glucocorticoid-induced TNF receptor-related protein, proinflammatory mediators, and cytokines in carrageenan-induced lung inflammation. J. Med. Chem., 2015, 58(22), 8850-8867.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00934] [PMID: 26456029]
[28]
Sangshetti, J.N.; Chabukswar, A.R.; Shinde, D.B. Microwave assisted one pot synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazoles as antifungal agents. Bioorg. Med. Chem. Lett., 2011, 21(1), 444-448.
[http://dx.doi.org/10.1016/j.bmcl.2010.10.120] [PMID: 21095127]
[29]
Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J.T.; Bokesch, H.; Kenney, S.; Boyd, M.R. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 1990, 82(13), 1107-1112.
[http://dx.doi.org/10.1093/jnci/82.13.1107] [PMID: 2359136]
[30]
Boyd, M.R.; Paull, K.D. Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev. Res., 1995, 34, 91-109.
[http://dx.doi.org/10.1002/ddr.430340203]
[31]
Monks, A.; Scudiero, D.; Skehan, P.; Shoemaker, R.; Paull, K.; Vistica, D.; Hose, C.; Langley, J.; Cronise, P.; Vaigro-Wolff, A.; Gray-Goodrich, M.; Campbell, H.; Mayo, J.; Boyd, M. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J. Natl. Cancer Inst., 1991, 83(11), 757-766.
[http://dx.doi.org/10.1093/jnci/83.11.757] [PMID: 2041050]
[32]
Shoemaker, R.H. The NCI60 human tumour cell line anticancer drug screen. Nat. Rev. Cancer, 2006, 6(10), 813-823.
[http://dx.doi.org/10.1038/nrc1951] [PMID: 16990858]
[34]
Koleva, I.I.; van Beek, T.A.; Linssen, J.P.; de Groot, A.; Evstatieva, L.N. Screening of plant extracts for antioxidant activity: a comparative study on three testing methods. Phytochem. Anal., 2002, 13(1), 8-17.
[http://dx.doi.org/10.1002/pca.611] [PMID: 11899609]

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