Abstract
Background: Acquired immunodeficiency syndrome (AIDS) and cancer treatment have been a major task for research scientists and pharmaceutical industry for the last many years. Seeking to the development, many promising chemical entities especially five-membered heterocyclic rings like oxadiazole have revealed good anticancer and anti HIV activities. The current review enlists some recently developed anti-HIV and anti-cancer oxadiazole moieties.
Methods: on the basis of structural modification for the syntheses of new oxadiazole analogs, the new anti-HIV and anti-cancer agents have been summarized, which can improve treatment of AIDs and cancer.
Results: The oxadiazole ring is more potent in comparison to some other heterocyclic rings (five and six membered) towards anti-HIV and anti-cancer activities. The important mechanisms involved for anti HIV and anticancer activity are mainly inhibition of enzymes like protease, HIV-integrase, telomerase, histone deacetylase, methionine amino peptidase, thymidylate synthase and focal adhesion kinase and inhibition of some growth factors.
Conclusion: By reviving the past literature about 50 most potent oxadiazole derivatives, depending upon activity and structural modifications, have been selected as potent anti-HIV, and anti-cancer agents. Thus, oxadiazole seems to be a ‘privileged structure’ for further screening and syntheses of the new drug analogs against life threatening HIV and cancer like diseases.
Keywords: Oxadiazole, anti-HIV, cancer, heterocyclic compounds, drug discovery, HIV–integrase inhibitor raltegravir, antiproliferative activity.
Graphical Abstract
[1]
Kumar, D.; Judge, V.; Narang, R.; Sangwan, S.; De Clercq, E.; Balzarini, J.; Narasimhan, B. Benzylidene/2-chlorobenzylidene hydrazides: synthesis, antimicrobial activity, QSAR studies and antiviral evaluation. Eur. J. Med. Chem., 2010, 45(7), 2806-2816.
[2]
De Clercq, E. Highlights in the development of new antiviral agents. Mini Rev. Med. Chem., 2002, 2(2), 163-175.
[3]
Kumar, D.; Kumar, V.; Mundlia, J.; Pradhan, D.; Malik, S. Thiazolidin-4-one derivatives as central nervous system potential agents. Cent. Nerv. Syst. Agents Med. Chem., 2015, 15, 23-27.
[4]
Liu, Z.; Chen, W.; Zhan, P.; Clercq, D.E.; Pannecouque, C.; Design, X.L. Synthesis and anti-HIV evaluation of novel diarylnicotinamide derivatives targeting the entrance channel of the NNRTI binding pocket through structure-guided molecular hybridization. Eur. J. Med. Chem., 2014, 87, 52-62.
[5]
Patel, M.B.; Modi, N.R.; Raval, J.P.; Menon, S.K. Calix[4]arene based 1,3,4-oxadiazole and thiadiazole derivatives: design, synthesis, and biological evaluation. Org. Biomol. Chem., 2012, 10(9), 1785-1794.
[6]
Benmansour, F.; Eydoux, C.; Querat, G.; de Lamballerie, X.; Canard, B.; Alvarez, K.; Guillemot, J.C.; Barral, K. Novel 2-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,3,4-oxadiazole and 3-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,2,4-oxadiazole derivatives as dengue virus inhibitors targeting NS5 polymerase. Eur. J. Med. Chem., 2016, 109, 146-156.
[7]
Thomas, S.J.; Endy, T.P. Current issues in dengue vaccination. Curr. Opin. Infect. Dis., 2013, 26(5), 429-434.
[8]
Savarino, A. A historical sketch of the discovery and development of HIV-1 integrase inhibitors. Expert Opin. Investig. Drugs, 2006, 15(12), 1507-1522.
[10]
Kumar, D.; Kapoor, A.; Kumar, P.; Thangadurai, A.; Narasimhan, B. Synthesis, antimicrobial evaluation and QSAR studies of 3-ethoxy-4-hydroxybenzylidene/4-nitrobenzylidene hydrazides. Chin. Chem. Lett., 2011, 22(11), 1293-1296.
[11]
Mickevičius, V.; Vaickelionienė, R.; Sapijanskaitė, B. Synthesis of substituted 1,3,4- oxadiazole derivatives. Chem. Heterocycl. Compd., 2009, 45, 215-218.
[12]
El Sadek, M.M.; Hassan, S.Y.; Abdelwahab, H.E.; Yacout, G.A. Synthesis and bioassay of a new class of furanyl-1,3,4-oxadiazole derivatives. Molecules, 2013, 18(7), 8550-8562.
[13]
Holla, B.S.; Poojary, K.N.; Bhat, K.S.; Ashok, M.; Poojary, B. Synthesis and anticancer activity studies on some 2-chloro-1,4-bis-(5- substituted-1,3,4-oxadiazol-2-ylmethyleneoxy) phenylene derivatives. Org. Med. Chem., 2005, 44(8), 1669-1673.
[14]
Ouyang, X.; Piatnitski, E.L.; Pattaropong, V.; Chen, X.; He, H.Y.; Kiselyov, A.S.; Velankar, A.; Kawakami, J.; Labelle, M.; Smith, L., II; 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.
[15]
Steigbigel, R.T.; Cooper, D.A.; Kumar, P.N.; Eron, J.E.; Schechter, M.; Markowitz, M.; Loutfy, M.R.; Lennox, J.L.; Gatell, J.M.; Rockstroh, J.K.; Katlama, C.; Yeni, P.; Lazzarin, A.; Clotet, B.; Zhao, J.; Chen, J.; Ryan, D.M.; Rhodes, R.R.; Killar, J.A.; Gilde, L.R.; Strohmaier, K.M.; Meibohm, A.R.; Miller, M.D.; Hazuda, D.J.; Nessly, M.L.; DiNubile, M.J.; Isaacs, R.D.; Nguyen, B.Y.; Teppler, H. Raltegravir with optimized background therapy for resistant HIV-1 infection. N. Engl. J. Med., 2008, 359(4), 339-354.
[16]
Zareef, M.; Iqbal, R.; Al-Masoudi, N.A.; Zaidi, J.H.; Arfan, M.; Shahzad, S. Synthesis, AntiHIV, and Antifungal Activity of New Benzensulfonamides Bearing the 2, 5-Disubstituted-1, 3, 4-Oxadiazole Moiety. Phosphorus Sulfur Silicon Relat. Elem., 2007, 182(2), 281-298.
[17]
Iqbal, R.; Zareef, M.; Ahmed, S.; Zaidi, J.H.; Arfan, M. Shafiqueb. M.; Al-Masoudic, N. A. Synthesis, Antimicrobial and Anti-HIV Activity of Some Novel Benzenesulfonamides Bearing 2, 5-Disubstituted-1, 3, 4-oxadiazole Moiety. J. Chin. Chem. Soc. (Taipei), 2006, 53, 689-696.
[18]
Jorgensen, W.L. Computer-aided discovery of anti-HIV agents. Bioorg. Med. Chem., 2016, 24(20), 4768-4778.
[19]
Abdel-Aziz, M. Abuo-Rahma, Gel-D.; Hassan, A.A. Synthesis of novel pyrazole derivatives and evaluation of their antidepressant and anticonvulsant activities. Eur. J. Med. Chem., 2009, 44(9), 3480-3487.
[20]
Almasirad, A.; Tabatabai, S.A.; Faizi, M.; Kebriaeezadeh, A.; Mehrabi, N.; Dalvandi, A.; Shafiee, A. Synthesis and anticonvulsant activity of new 2-substituted-5- [2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-triazoles. Bioorg. Med. Chem. Lett., 2004, 14(24), 6057-6059.
[21]
Manjunatha, K.; Poojary, B.; Lobo, P.L.; Fernandes, J.; Kumari, N.S. Synthesis and biological evaluation of some 1,3,4-oxadiazole derivatives. Eur. J. Med. Chem., 2010, 45(11), 5225-5233.
[22]
Shailaja, M.; Anitha, M.; Manjula, A.; Rao, B.V. Synthesis and biological activity of novel 2,5-disubstituted-l,3,4- oxadiazoles. Indian J. Chem., 2010, 49(8), 1088-1097.
[23]
Mulwad, V.V.; Chaskar, A.C. Synthesis and antibacterial activity of new oxadiazolo[1,3,5]-triazine, 1,2,4 triazolo and thiadiazolo 1,3,4 oxadiazole derivatives. ChemInform, 2006, 45(7), 1710-1715.
[24]
Ansari, K.F.; Lal, C. Synthesis and evaluation of some new benzimidazole derivatives as potential antimicrobial agents. Eur. J. Med. Chem., 2009, 44(5), 2294-2299.
[25]
Dewangan, D.; Pandey, A.; Sivakumar, T.; Rajavel, R.; Dubey, R.D. Synthesis of some Novel 2, 5-Disubstituted 1, 3, 4-oxadiazole and its analgesic, anti-inflammatory, anti-bacterial and anti-tubercular activity. Int. J. Chemtech Res., 2010, 3(3), 1397-1412.
[26]
Bhandari, S.V.; Bothara, K.G.; Raut, M.K.; Patil, A.A.; Sarkate, A.P.; Mokale, V.J. Design, synthesis and evaluation of antiinflammatory, analgesic and ulcerogenicity studies of novel S-substituted phenacyl-1,3,4-oxadiazole-2-thiol and Schiff bases of diclofenac acid as nonulcerogenic derivatives. Bioorg. Med. Chem., 2008, 16(4), 1822-1831.
[27]
Ali, M.A.; Shaharyar, M. Oxadiazole mannich bases: synthesis and antimycobacterial activity. Bioorg. Med. Chem. Lett., 2007, 17(12), 3314-3316.
[28]
Ogata, M.; Atobe, H.; Kushida, H.; Yamamoto, K. In vitro sensitivity of mycoplasmas isolated from various animals and sewage to antibiotics and nitrofurans. J. Antibiot. (Tokyo), 1971, 24(7), 443-451.
[29]
Vardan, S.; Smulyan, H.; Mookherjee, S.; Eich, R. Effects of tiodazosin, a new antihypertensive, hemodynamics and clinical variables. Clin. Pharmacol. Ther., 1983, 34(3), 290-296.
[30]
Schlecker, R.; Thieme, P.C. The synthesis of antihypertensive 3-(1, 3, 4-oxadiazol-2-yl) phenoxypropanolamines. Tetrahedron, 1988, 44(11), 3289-3294.
[31]
Patel, M.B.; Modi, N.R.; Raval, J.P.; Menon, S.K. Calix[4]arene based 1,3,4-oxadiazole and thiadiazole derivatives: design, synthesis, and biological evaluation. Org. Biomol. Chem., 2012, 10(9), 1785-1794.
[32]
Shaik, B.; Agrawal, V.; Gupta, S.P.; Menon, U. Quantitative structure-activity relationship and docking studies on a series of oxadiazole and triazole substituted naphthyridines as HIV-1 integrase inhibitors. Lett. Drug Des. Discov., 2017, 4(1), 10-27.
[33]
Tan, T.M.C.; Chen, Y.; Kong, K.H.; Bai, J.; Li, Y.; Lim, S.G.; Ang, T.H.; Lam, Y. Synthesis and the biological evaluation of 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles as potential anti-hepatitis B virus agents. Antiviral Res., 2006, 71(1), 7-14.
[34]
Abu-Zaied, M.A.; El-Telbani, E.M.; Elgemeie, G.H.; Nawwar, G.A.M. Synthesis and in vitro anti-tumor activity of new oxadiazole thioglycosides. Eur. J. Med. Chem., 2011, 46(1), 229-235.
[35]
Liu, K.; Lu, H.; Hou, L.; Qi, Z.; Teixeira, C.; Barbault, F.; Fan, B.T.; Liu, S.; Jiang, S.; Xie, L. Design, synthesis, and biological evaluation of N-carboxyphenylpyrrole derivatives as potent HIV fusion inhibitors targeting gp41. J. Med. Chem., 2008, 51(24), 7843-7854.
[36]
Zarghi, A.; Hajimahdi, Z. Substituted oxadiazoles: a patent review (2010 - 2012). Expert Opin. Ther. Pat., 2013, 23(9), 1209-1232.
[37]
Kaur, H.; Saini, S.; Peer, S.; Singh, J. Current therapies and novel targets in treatment of breast cancer. Sys Rev Pharm, 2010, 1(1), 40-49.
[38]
Bajaj, S.; Asati, V.; Singh, J.; Roy, P.P. 1,3,4-Oxadiazoles: An emerging scaffold to target growth factors, enzymes and kinases as anticancer agents. Eur. J. Med. Chem., 2015, 97(5), 124-141. 1,3,4- Oxadiazoles: An emerging scaffold to target growth factors, enzymes and kinases as anticancer agents
[39]
Mochona, B.; Qi, X.; Euynni, S.; Sikazwi, D.; Mateeva, N.; Soliman, K.F. Design and evaluation of novel oxadiazole derivatives as potential prostate cancer agents. Bioorg. Med. Chem. Lett., 2016, 26(12), 2847-2851.
[40]
Che, Z.; Liu, S.; Tian, Y.; Hu, Z.; Chen, Y.; Chen, G. Design and synthesis of novel N-Arylsulfonyl-3-(2-yl-ethanone)-6-methylindole derivatives as inhibitors of HIV-1 replication. Pharmaceuticals (Basel), 2015, 8(2), 221-229.
[41]
Sun, J.; Li, M.; Quin, S.S.; Guo, F.J.; Dang, X.F.; Wang, X.M.; Xue, Y.R.; Zhu, H.L. Synthesis and antitumor activity of 1,3,4-oxadiazole possessing 1,4-benzodioxan moiety as a novel class of potent methionine aminopeptidase type II inhibitors. Bioorg. Med. Chem. Lett., 2013, 23(10), 2876-2879.
[42]
Manal, M.; Chandrasekar, M.J.N.; Gomathi Priya, J.; Nanjan, M.J. Inhibitors of histone deacetylase as antitumor agents: A critical review. Bioorg. Chem., 2016, 67, 18-42.
[43]
Sakamoto, T.; Cullen, M.D.; Hartman, T.L.; Watson, K.M.; Buckheit, R.W.; Pannecouque, C.; De Clercq, E.; Cushman, M. Synthesis and anti-HIV activity of new metabolically stable alkenyldiarylmethane non-nucleoside reverse transcriptase inhibitors incorporating N-methoxy imidoyl halide and 1,2,4-oxadiazole systems. J. Med. Chem., 2007, 50(14), 3314-3321.
[44]
El-Sayed, W.A.; El-Essawy, F.A.; Ali, O.M.; Nasr, B.S.; Abdalla, M.M.; Abdel-Rahman, A.A. Anti-HIV activity of new substituted 1,3,4-oxadiazole derivatives and their acyclic nucleoside analogues. Z. Natforsch. C J. Biosci., 2009, 64(11-12), 773-778.
[45]
Wang, Z.; Wang, M.; Yao, X.; Li, Y.; Qiao, W.; Geng, Y.; Liu, Y.; Wang, Q. Hydroxyl may not be indispensable for raltegravir: Design, synthesis and SAR Studies of raltegravir derivatives as HIV-1 inhibitors. Eur. J. Med. Chem., 2012, 50, 361-369.
[46]
El-Emam, A.A.; Al-Deeb, O.A.; Al-Omar, M.; Lehmann, J. Synthesis, antimicrobial, and anti-HIV-1 activity of certain 5-(1-adamantyl)-2-substituted thio-1,3,4-oxadiazoles and 5-(1-adamantyl)-3-substituted aminomethyl-1,3,4-oxadiazoline-2-thiones. Bioorg. Med. Chem., 2004, 12(19), 5107-5113.
[47]
Iqbal, R.; Zareef, M.; Ahmed, S.; Zaidi, J.H.; Arfan, M.; Shafique, M.; Al-masoudi, N.A. Synthesis, antimicrobial and anti-HIV activity of some novel benzenesulfonamides bearing 2,5-disubstituted-1,3,4-oxadiazole moiety. J. Chin. Chem. Soc. (Taipei), 2006, 53, 689-696.
[48]
Kim, R.M.; Rouse, E.A.; Chapman, K.T.; Schleif, W.A.; Olsen, D.B.; Stahlhut, M.; Rutkowski, C.A.; Emini, E.A.; Tata, J.R. P1′ oxadiazole protease inhibitors with excellent activity against native and protease inhibitor-resistant HIV-1. Bioorg. Med. Chem. Lett., 2004, 14(18), 4651-4654.
[49]
Syed, T.; Akhtar, T.; Al-Masoudi, N.A.; Jones, P.G.; Hameed, S. Synthesis, QSAR and anti-HIV activity of new 5-benzylthio-1,3,4-oxadiazoles derived from α-amino acids. J. Enzyme Inhib. Med. Chem., 2011, 26(5), 668-680.
[50]
Zhang, F.; Wang, X.L.; Shi, J.; Wang, S.F.; Yin, Y.; Yang, Y.S.; Zhang, W.M.; Zhu, H.L. Synthesis, molecular modeling and biological evaluation of N-benzylidene-2-((5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl)thio)acetohydrazide derivatives as potential anticancer agents. Bioorg. Med. Chem., 2014, 22(1), 468-477.
[51]
Ramazani, A.; Khoobi, M.; Torkaman, A.; Nasrabadi, F.Z.; Forootanfar, H.; Shakibaie, M.; Jafari, M.; Ameri, A.; Emami, S.; Faramarzi, M.A.; Foroumadi, A.; Shafiee, A. One-pot, four-component synthesis of novel cytotoxic agents 1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines. Eur. J. Med. Chem., 2014, 78, 151-156.
[52]
Sun, J.; Zhu, H.; Yang, Z.M.; Zhu, H.L. Synthesis, molecular modeling and biological evaluation of 2-aminomethyl-5-(quinolin-2-yl)-1,3,4-oxadiazole-2(3H)-thione quinolone derivatives as novel anticancer agent. Eur. J. Med. Chem., 2013, 60, 23-28.
[53]
Gurupadaswamy, H.D.; Girish, V.; Kavitha, C.V.; Raghavan, S.C.; Khanum, S.A. Synthesis and evaluation of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles as anti-cancer agents. Eur. J. Med. Chem., 2013, 63, 536-543.
[54]
Rapolu, S.; Alla, M.; Bommena, V.R.; Murthy, R.; Jain, N.; Bommareddy, V.R.; Bommineni, M.R. Synthesis and biological screening of 5-(alkyl(1H-indol-3-yl))-2-(substituted)-1,3,4-oxadiazoles as antiproliferative and anti-inflammatory agents. Eur. J. Med. Chem., 2013, 66, 91-100.
[55]
Ahsan, M.J.; Rathod, V.P.S.; Singh, M.; Sharma, R.; Jadav, S.S.; Yasmin, S.; Kumar, S.; Kumar, P. Synthesis, anticancer and molecular docking studies of 2-(4-chlorophenyl)-5-aryl-1, 3, 4- oxadiazole analogues. Med. Chem., 2013, 3(4), 294-297.
[56]
Brożewicz, K.; Sławiński, J. 1-(2-Mercaptobenzenesulfonyl)-3-hydroxyguanidines--novel potent antiproliferatives, synthesis and in vitro biological activity. Eur. J. Med. Chem., 2012, 55, 384-394.
[57]
Puthiyapurayil, P.; Poojary, B.; Chikkanna, C.; Buridipad, S.K. Design, synthesis and biological evaluation of a novel series of 1,3,4-oxadiazole bearing N-methyl-4-(trifluoromethyl)phenyl pyrazole moiety as cytotoxic agents. Eur. J. Med. Chem., 2012, 53, 203-210.
[58]
Rashid, M.; Husain, A.; Mishra, R. Synthesis of benzimidazoles bearing oxadiazole nucleus as anticancer agents. Eur. J. Med. Chem., 2012, 54, 855-866.
[59]
Bondock, S.; Adel, S.; Etman, H.A.F.; Badria, F.A. Synthesis and antitumor evaluation of some new 1,3,4-oxadiazole-based heterocycles. Eur. J. Med. Chem., 2012, 48, 192-199.
[60]
Luo, Z.H.; He, S.Y.; Chen, B.Q.; Shi, Y.P.; Liu, Y.M.; Li, C.W.; Wang, Q.S. Synthesis and in vitro antitumor activity of 1,3,4-oxadiazole derivatives based on benzisoselenazolone. Chem. Pharm. Bull. (Tokyo), 2012, 60(7), 887-891.
[61]
Kashaw, S.K.; Kumar, A.; Gupta, A.; Kashaw, V.; Shukla, G.; Mishra, V. Synthesis and anticancer evaluation of some novel 3-[5-(4-substituted)phenyl-1,3,4-oxadiazol-2-yl]-2- Phenylquinazolin-4(3H)-ones. Int. J. Pharma Sci., 2012, 4, 502-506.
[62]
Ren, J.; Wu, L.; Xin, W.Q.; Chen, X.; Hu, K. Synthesis and biological evaluation of novel 4β-(1,3,4-oxadiazole-2-amino)-podophyllotoxin derivatives. Bioorg. Med. Chem. Lett., 2012, 22(14), 4778-4782.
[63]
Gudipati, R.; Anreddy, R.N.R.; Manda, S. Synthesis, characterization and anticancer activity of certain 3-4-(5-mercapto-1, 3, 4-oxadiazol-2-yl)phenyliminoindolin-2-one derivatives. Saudi Pharm. J., 2011, 19, 153-158.
[64]
Zhang, X.M.; Qiu, M.; Sun, J.; Zhang, Y.B.; Yang, Y.S.; Wang, X.L.; Tang, J.F.; Zhu, H.L. Synthesis, biological evaluation, and molecular docking studies of 1,3,4-oxadiazole derivatives possessing 1,4-benzodioxan moiety as potential anticancer agents. Bioorg. Med. Chem., 2011, 19(21), 6518-6524.
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Analytical Chemistry
Current Computer-Aided Drug Design
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Related Books
Drug Addiction Mechanisms in the Brain
Botanicals and Natural Bioactives: Prevention and Treatment of Diseases
Software and Programming Tools in Pharmaceutical Research
Objective Pharmaceutics: A Comprehensive Compilation of Questions and Answers for Pharmaceutics Exam Prep
Biotechnology and Drug Development for Targeting Human Diseases
Biosurfactants: A Boon to Healthcare, Agriculture & Environmental Sustainability
Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems
Frontiers in Computational Chemistry
Enzymatic Targets for Drug Discovery Against Alzheimer's Disease
Advances in Dye Degradation
Article Metrics
90
2
