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Synthesis, Anticancer Activity and Computational Docking Techniques of Some Novel Derivatives Based on Indole Bearing Oxadiazole–Triazole Moieties

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Abstract

In this study, a new series of 1,4-disubstituted-1,2,3-triazole and 2,5-disubstituted oxadiazole tethered indole compounds were synthesized and their molecular structures were characterized by using 1H NMR, 13C NMR, FT–IR, mass and elemental analysis techniques. In particular 3-chloro-5-fluorophenyl-1,2,3-triazolylacetamide-1,3,4-oxadiazole, 2,6-difluorophenyl-triazolyloxadiazole, 4-trifluoromethylphenyl-triazolyloxadiazole had IC50 range 3.2–3.8 μg/mL against MCF-7 whereas 2,6-difluorophenyl-1,2,3-triazole-1,3,4-oxadiazole linked indole, 4-trifluoromethylphenyl-triazolyloxadiazole, 2-nitrophenyl-1,2,3-triazolyl-1,3,4-oxadiazole, 2,5-dimethoxyphenyl-1,2,3-triazolyl-1,3,4-oxadiazole and 3-chloro-5-fluorophenyl-triazolyloxadiazole, 3-chloro-5-fluorophenyl-1,2,3-triazolylacetamide-1,3,4-oxadiazole are active against MDA-MB-468 cell line with IC50 3.2–8.1 μg/mL respectively. Notably 3-chloro-5-fluorophenyl-1,2,3-triazolylacetamide-1,3,4-oxadiazole, 4-trifluoromethylphenyl-triazolyloxadiazole exhibited highest amino acid bonding interactions like AspA:124, ArgA:189, AspA:173, AsnA:69, LysA:168 (2), SerA:171, ArgA:75, Ala:44, LysA:52, GluA:72, TyrA:193, ThrA:48, LysA:47, GluA:72, ArgA:74. Final scaffolds p-tolyl-1,2,3-triazolyl-1,3,4-oxadiazole, 2,6-difluorophenyl-1,2,3-triazole-1,3,4-oxadiazole, 4-fluorobenzyl-1,2,3-triazolyl-1,3,4-oxadiazole, and 3,5-dichlorophenyl-1,2,3-triazolyl-1,3,4-oxadiazoles acquiring highest potency drug-likeness properties and processing Lipinski’s rule of five as good oral bioavailability agents.

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REFERENCES

  1. Torre, L.A., Bray, F., Siegel, R.L., Ferlay, J., Lortet Tieulent, J., and Jemal, A., CA Cancer J. Clin., 2015, vol. 65, pp. 87–108. https://doi.org/10.3322/caac.21262

    Article  PubMed  Google Scholar 

  2. Prat, A., Pineda, E., Adamo, B., Galvan, P., Fernandez, A., Gaba, L., Diez, M., Viladot, M., Arance, A., and Munoz, M., Breast, 2015, vol. 24, pp. S26–S35. https://doi.org/10.1016/j.breast.2015.07.008

    Article  PubMed  Google Scholar 

  3. Queiroz, M.J., Abreu, A.S., Carvalho, M.S., Ferreira, P.M., Nazareth, N., and Sao Jose Nascimento, M., Bioorg. Med. Chem., 2008, vol. 16, pp. 5584–5589. https://doi.org/10.1016/j.bmc.2008.04.004

    Article  CAS  PubMed  Google Scholar 

  4. Yusuf, M.A., Ali, M.Q., Mustafa, M.E., and Wolfgang, V., Monatshefte Chem., 2006, vol. 137, pp. 243–248. https://doi.org/10.1007/s00706-005-0424-6

    Article  CAS  Google Scholar 

  5. Thirumurugan, P., Mahalaxmi, S., and Perumal, P.T., J. Chem. Sci., 2010, vol. 122, pp. 819–832. https://doi.org/10.1007/s12039-010-0070-3

    Article  CAS  Google Scholar 

  6. Silveira, C.C., Mendes, S.R., Soares, J.R., Victoria, F.N., Martinez, D.M., and Savegnago, L., Tetrahedron Lett., 2013, vol. 54, pp. 4926–4929. https://doi.org/10.1016/j.tetlet.2013.07.004

    Article  CAS  Google Scholar 

  7. Sanna, G., Madeddu, S., Giliberti, G., Piras, S., Struga, M., Wrzosek, M., Kubiak T. G., Koziol, A.E., Savchenko, O., Lis, T., and Stefanska, J., Molecules, 2018, vol. 23, p. 2554. https://doi.org/10.3390/molecules23102554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yang, D., Wang, P., Liu, J., Xing, H., Liu, Y., Xie, W., and Zhao, G., Bioorg. Med. Chem., 2014, vol. 22, pp. 366–373. https://doi.org/10.1016/j.bmc.2013.11.022

  9. Karali, N., Gursoy, A., Kandemirli, F., Shvets, N., Kaynak, F.B., and Ozbey, S., Bioorg. Med. Chem., 2007, vol. 15, pp. 5888–5904. https://doi.org/10.1016/j.bmc.2007.05.063

    Article  CAS  PubMed  Google Scholar 

  10. Zheng, M., Zheng, M., Ye, D., Deng, Y., Qiu, S., Luo, X., Chena, K., Liua, H., and Jiangac, H., Bioorg. Med. Chem. Lett., 2007, vol. 17, pp. 2414–2420. https://doi.org/10.1016/j.bmcl.2007.02.038

    Article  CAS  PubMed  Google Scholar 

  11. Xu, H. and Fan, L.L., Eur. J. Med. Chem., 2011, vol. 46, pp. 364–369. https://doi.org/10.1016/j.ejmech.2010.10.022

    Article  CAS  PubMed  Google Scholar 

  12. Kasralikar, H.M., Jadhavar, S.C., and Bhusare, S.R., Bioorg. Med. Chem. Lett., 2015, vol. 25, pp. 3882–3886. https://doi.org/10.1016/j.bmcl.2015.07.050

    Article  CAS  PubMed  Google Scholar 

  13. Han, X., Wu, H., Wang, W., Dong, C., Tien, P., Wu, S., and Zhou, H.B., Org. Biomol. Chem., 2014, vol. 12, pp. 8308–8317. https://doi.org/10.1039/C4OB01333F

    Article  CAS  PubMed  Google Scholar 

  14. Kaur, H., Singh, J., and Narasimhan, B., BMC Chem., 2019, vol. 13, p. 65. https://doi.org/10.1186/s13065-019-0580-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gu, X.H., Wan, X.Z., and Jiang, B., Bioorg. Med. Chem. Lett., 1999, vol. 22, pp. 569–572. https://doi.org/10.1016/S0960-894X(99)00037-2

    Article  Google Scholar 

  16. Casapullo, A., Bifulco, G., Bruno, I., and Riccio, R., J. Nat. Prod., 2000, vol. 63, pp. 447–451. https://doi.org/10.1021/np9903292

    Article  CAS  PubMed  Google Scholar 

  17. Cohen, J., Paul, G., Gunasekera, S., Longley, R., and Pomponi, S., Discodermia polydiscus. Pharmaceut. Biol., 2004, vol. 42, pp. 59–61. https://doi.org/10.1080/13880200490505546

    Article  CAS  Google Scholar 

  18. Kawasaki, I., Yamashita, M., and Ohta, S., Chem. Commun., 1994, vol. 18, pp. 2085–2086. https://doi.org/10.1039/C39940002085

    Article  Google Scholar 

  19. Nakagawa, M., Nagata, T., Ono, K., Uchida, H., Watanabe, T., Hatakeyama, K., Akiba, M., Fuwa, M., Arisawa, M., and Nishida, A., Adv. Exp. Med. Biol., 2003, vol. 527, pp. 609–620. https://doi.org/10.1007/978-1-4615-0135-0_70

    Article  CAS  PubMed  Google Scholar 

  20. Chavan Rajashree, S. and More Harinath, N., J. Pharm. Res., 2011, vol. 4, pp. 1575–1578. https://doi.org/10.4236/ijoc.2015.52010

    Article  CAS  Google Scholar 

  21. Steffan, N., Grundmann, A., Yin, W.B., Kremer, A., and Li, S.M., Curr. Med. Chem., 2009, vol. 16, pp. 218–231. https://doi.org/10.2174/092986709787002772

    Article  CAS  PubMed  Google Scholar 

  22. Ma, J., Bao, G., Wang, L., Li, W., Xu, B., Du, B., Lv, J., Zhai, X., and Gong, P., Eur. J. Med. Chem., 2015, vol. 96, pp. 173–186. https://doi.org/10.1016/j.ejmech.2015.04.018

    Article  CAS  PubMed  Google Scholar 

  23. Hong, B.C., Jiang, Y.F., Chang, Y.L., and Lee, S.J., J. Chin. Chem. Soc., 2006, vol. 53, pp. 647–662. https://doi.org/10.1002/jccs.200600086

    Article  CAS  Google Scholar 

  24. Dalvie, D.K., Kalgutkar, A.S., Khojasteh-Bakht, S.C., Obach, R.S., and O’Donnell, J.P., Chem. Res. Toxicol., 2002, vol. 15, pp. 269–299. https://doi.org/10.1021/tx015574b

    Article  CAS  PubMed  Google Scholar 

  25. Havlicek, L., Fuksova, K., Krystof, V., Orsag, M., Vojtesek, B., and Strnad, M., Bioorg. Med. Chem., 2005, vol. 13, pp. 5399–5407. https://doi.org/10.1016/j.bmc.2005.06.007

    Article  CAS  PubMed  Google Scholar 

  26. Siva Kumar, G., Amit A. K., Tejeswara Rao, A., and Anjali, J., Chem. Select., 2022, vol. 21, p. e202200683. https://doi.org/10.1002/slct.202200683

    Article  CAS  Google Scholar 

  27. Lønning, P.E., Geisler, J., and Dowsett, M., Breast Cancer Res. Treat., 1998, vol. 49, pp. S53–S57. https://doi.org/10.1023/A:1006000806630

    Article  PubMed  Google Scholar 

  28. Sampath, B., Someswar Rao S., Ramulu D., Muralidhar Reddy, P., Saritha, B., Akkiraju, A.G., Vijaya Kumar, B., and Krisham Raju A., J. Mol. Struct., 2020, vol. 12, p. 128705. https://doi.org/10.1016/j.molstruc.2020.128705

    Article  CAS  Google Scholar 

  29. Wallace, D.J., Mangion, I., and Coleman, P., Am. Chem. Soc., 2016, vol. 1239, pp. 1–36. https://doi.org/10.1021/bk-2016-1239.ch001

    Article  CAS  Google Scholar 

  30. Kelley, J.L., Koble, C.S., Davis, R.G., McLean, E.W., Soroko, F.E., and Cooper, B.R., J. Med. Chem., 1995, vol. 38, pp. 4131–4134. https://doi.org/10.1021/jm00020a030

    Article  CAS  PubMed  Google Scholar 

  31. Oroumadi, A., Mansouri, S., Kiani, Z., and Rahmani, A., Eur. J. Med. Chem., 2003, vol. 38, pp. 851–854. https://doi.org/10.1016/s0223-5234(03)00148-x

    Article  Google Scholar 

  32. Mady, M.F., Awad, G.E.A., and Jørgensen, K.B., Eur. J. Med. Chem., 2014, vol. 84, pp. 433–443. https://doi.org/10.1016/j.ejmech.2014.07.042

    Article  CAS  PubMed  Google Scholar 

  33. Küçükgüzel, I., Küçükgüzel, S.G., Rollas, S., and Kiraz, M., Bioorg. Med. Chem. Lett., 2001, vol. 11, pp. 1703–1707. https://doi.org/10.1016/S0960-894X(01)00283-9

    Article  PubMed  Google Scholar 

  34. Bollu, R., Palem, J.D., Bantu, R., Guguloth, V., Nagarapu, L., Polepalli, S., and Jain, N., Eur. J. Med. Chem., 2014, vol. 89, pp. 138–146. https://doi.org/10.1016/j.ejmech.2014.10.051

    Article  CAS  PubMed  Google Scholar 

  35. Gao, F., Wang, T., Xiao, J., and Huang, G., Eur. J. Med. Chem., 2019, vol. 173, pp. 274–281. https://doi.org/10.1016/j.ejmech.2019.04.043

    Article  CAS  PubMed  Google Scholar 

  36. Zhang, M.Z., Mulholland, N., Beattie, D., Irwin, D., Gu, Y.C., Chen, Q., Guang Fu Y., and John, C. Eur. J. Med. Chem., 2013, vol. 63, pp. 22–32. https://doi.org/10.1016/j.ejmech.2013.01.038

    Article  CAS  PubMed  Google Scholar 

  37. Musad, A.E., Mohamad, R., Saeed, B.A., Viswanath, B.S., and Rai, K.M., Bioorg. Med. Chem. Lett., 2011, vol. 21, pp. 3536–3540. https://doi.org/10.1016/j.bmcl.2011.04.142

    Article  CAS  Google Scholar 

  38. Salahuddin, S., Mazumder, M., Ashan, A., and Jawed, M., Arab. J. Chem., 2014, vol. 7, pp. 418–424. https://doi.org/10.1016/j.arabjc.2013.02.001

    Article  CAS  Google Scholar 

  39. Hemalatha, G. and Sarangapani, M., Chin. Chem. Lett., 2013, vol. 24, pp. 127–130. https://doi.org/10.1016/j.cclet.2013.01.001

    Article  CAS  Google Scholar 

  40. Ping Yang, Jia-Bao Luo, Li-Lei Zhang, Ying-Si Wang, Xiao-Bao Xie, Qing-Shan Shi, and Xin-Guo Zhang, Chem. Select., 2021, vol. 6, pp. 13209–13214. https://doi.org/10.1002/slct.202103078

    Article  CAS  Google Scholar 

  41. Swarnagowri, N., Santosh L.G., Druti, H., Kiran C., Hari, G., Pai, K.S.R., Bharath Raja, G., and Sushruta, S.H., Chem. Biodiversity, 2022, vol. 19, p. e202100956. https://doi.org/10.1002/cbdv.202100956

    Article  CAS  Google Scholar 

  42. Caizhi, T., Shuoqi, H., Zihua, X., Wenwu, L., Deping, L., Mingyue, L., Chengze, Z., Limeng, W., Xiaowen, J., Huaiwei, D., and Qingchun, Z., Bioorg. Med. Chem. Lett., 2022, vol. 64, p. 128663. https://doi.org/10.1016/j.bmcl.2022.128663

    Article  CAS  Google Scholar 

  43. Rehman, A., Siddiqa, A., Abbasi, M.A., Rasool, S., Siddiqui, S.Z., Ahmad, I., and Saira A., Bull. Fac. Pharm. Cairo Univ., 2015, vol. 53, pp. 37–43. https://doi.org/10.1016/j.bfopcu.2014.10.001

    Article  Google Scholar 

  44. Ahsan, M.J., Samy, J.G., Khalilullah, H., Nomani, M.S., Saraswat, P., and Singh, G.R., Bioorg. Med. Chem. Lett., 2011, vol. 21, pp. 7246–7250. https://doi.org/10.1016/j.bmcl.2010.11.084

    Article  CAS  PubMed  Google Scholar 

  45. Harish, K.P., Mohana, K.N., Mallesha, L., and Kumar, B.N., Eur. J. Med. Chem., 2013, vol. 65, pp. 276–283. https://doi.org/10.1016/j.ejmech.2013.04.054

    Article  CAS  PubMed  Google Scholar 

  46. Dunga, A.K., Allaka, T.R., Kethavarapu, Y., Nechipadappu, S.K., Pothana, P., Kuppan, C., and Kishore, P.V., Curr. Org. Synth., 2022. https://doi.org/10.2174/1570179419666220822125724

  47. Tejeswara Rao, A, Bhaskar, K., Naveen, P., Naveen, K., Kalyani, C., and Jaya Shree, A., Mol. Diversity, 2022, vol. 26, pp.1581–1596. https://doi.org/10.1007/s11030-021-10287-3

    Article  CAS  Google Scholar 

  48. Nima, S., Maryam, M.K., Nafise, A., Samanesadat, H., Mahmood, B., Bagher, L., Mohammad, M., Haleh, H., Parham, T., Nastaran, S., and Ilhami, G., Arch. Pharm., 2020, p. e2000109. https://doi.org/10.1002/ardp.202000109

  49. Mosmann, T., J. Immunol. Methods, 1983, vol. 65, pp. 55–63. https://doi.org/10.1016/0022-1759(83)90303-4

    Article  CAS  PubMed  Google Scholar 

  50. Bose, D.S., Idrees, M., Jakka, N.M., and Rao, J.V., J. Comb. Chem., 2010, vol. 12, pp. 100–110. https://doi.org/10.1021/cc900129t

    Article  CAS  PubMed  Google Scholar 

  51. Kocemba, K.A., Dulinska Litewka, J., Wojdyła, K.L., and Pekala, P.A., Postepy. Hig. Med. Dosw., 2016, vol. 70, pp. 938–950. https://doi.org/10.5604/17322693.1218187

    Article  Google Scholar 

  52. Yalcin, A., Telang, S., Clem, B., and Chesney, J., Exp. Mol. Pathol., 2009, vol. 86, pp. 174–179. https://doi.org/10.1016/j.yexmp.2009.01.003

    Article  CAS  PubMed  Google Scholar 

  53. Okar, D.A., Manzano, A., Navarro Sabate, A., Riera, L., Bartrons, R., and Lange, A.J. Trends Biochem, Sci., 2001, vol. 26, pp. 30–35. https://doi.org/10.1016/S0968-0004(00)01699-6

    Article  CAS  PubMed  Google Scholar 

  54. Boutard, N., Bialas, A., Sabiniarz, A., Guzik, P., Banaszak, K., Biela, A., Bien, M., Buda, A., Bugaj, B., Cieluch, E., Cierpich, A., Dudek, L., Eggenweiler, H.M., Fogt, J., Gaik, M., Gondela, A., Jakubiec, K., Jurzak, M., Kitlinska, A., Kowalczyk, P., Kujawa, M., Kwiecinska, K., Les, M., Lindemann, R., Maciuszek, M., Mikulski, M., Niedziejko, P., Obara, A., Pawlik, H., Rzymski, T., Sieprawska-Lupa, M., Sowinska, M., Szeremeta-Spisak, J., Stachowicz, A., Tomczyk, M.M., Wiklik, K., Wloszczak, L., Ziemianska, S., Zarebski, A., Brzozka, K., Nowak, M., and Fabritius, C.H., Bioorg. Med. Chem. Lett., 2019, vol. 29, pp. 646–653. https://doi.org/10.1016/j.bmcl.2018.12.034

    Article  CAS  PubMed  Google Scholar 

  55. O’Boyle, N.M., Banck, M., and James, C.A., J. Chem. Inf., 2011, vol. 3, p. 33. https://doi.org/10.1186/1758-2946-3-33

    Article  CAS  Google Scholar 

  56. Ananda Kumar, D., Tejeswara Rao, A., Yugandhar, K., Sunil Kumar, N., Pradeep, P., Kishore, R., Jajula, K., and Kishore, P.V.V.N., Results Chem., 2022, vol. 4, p. 100605. https://doi.org/10.1016/j.rechem.2022.100605

    Article  CAS  Google Scholar 

  57. Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., and Olson, A.J., J. Comput. Chem., 2009, vol. 16, pp. 2785–2791. https://doi.org/10.1002/jcc.21256

    Article  CAS  Google Scholar 

  58. Nam, Q.H.D., Ngan, T.K., Nguyen, V.B., Duong, H.T.T., Nguyen, L.B., Vong, D.N., Duong, N.T.T., Nguyen, T.L.T., Nguyen, T.T.H., and Do, T.N.T., ACS Omega, 2022, vol. 7, pp. 33963−33984. https://doi.org/10.1021/acsomega.2c02933

  59. Veber, D.F., Johnson, S.R., Cheng, H.Y., Smith, B.R., Ward, K.W., and Kapple, K.D., J. Med. Chem., 2002, vol. 45, pp. 2615–2623. https://doi.org/10.1021/jm020017n

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

One of the authors (GG) is thankful to Aragen Life Sciences for providing the required lab facilities and motivation for completion of the research work and special thanks to Koneru Lakshmaiah Education Foundation.

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Authors and Affiliations

  1. Department of Engineering Chemistry, College of Engineering, Koneru Lakshmaiah Education Foundation, 522302, Vaddeswaram, Andhra Pradesh, India

    Gopalarao Gogisetti, Umamaheswararao Kanna & Bhaskara Rao Tadiboina

  2. Medicinal Chemistry Division, Aragen Life Sciences Pvt. Ltd (Formerly called as GVK Biosciences PVT. Ltd.), 500076, Mallapur, Hyderabad, Telangana, India

    Gopalarao Gogisetti, Tejeswara Rao Allaka & Vishal Sharma

  3. Centre for Chemical Sciences and Technology, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad, 500085, Kukatpally, Hyderabad, Telangana, India

    Tejeswara Rao Allaka

  4. Department of Chemistry, GITAM Institute of Science, GITAM (Deemed to be University), Gandhi Nagar, Rushikonda, 530045, Visakhapatnam, Andhra Pradesh, India

    Sravanthi Basireddy & Ravi Kumar Ganta

  5. Department of Chemistry, Institute of Aeronautical Engineering, 500043, Dundigal, Hyderabad, Telangana, India

    Sravanthi Basireddy

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General experimental details and characterization data of all the remaining synthesised scaffolds, general procedure for their biological activity and docking studies, and copies of 1H NMR, 13C NMR, IR and mass spectrums are included in supporting information.

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Gopalarao Gogisetti, Allaka, T.R., Kanna, U. et al. Synthesis, Anticancer Activity and Computational Docking Techniques of Some Novel Derivatives Based on Indole Bearing Oxadiazole–Triazole Moieties. Russ J Bioorg Chem 49, 629–644 (2023). https://doi.org/10.1134/S1068162023030111

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