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Rational synthesis, anticancer activity, and molecular docking studies of novel benzofuran liked thiazole hybrids

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Abstract

A novel series of benzofuran bearing thiazole hybrids were synthesized by the multistep reaction approach. All synthesized molecules were selected by the National Cancer Institute, USA for one-dose anticancer activity against 60 various human cancer cell lines indicating nine types of cancer. Among thirteen compounds, two compounds showed higher lethality, so, it was selected for five-dose anticancer screening against all cancer cell lines. Compound 8g and 8h were displayed remarkable antiproliferative activity with GI50 values ranging from 0.295 to 4.15 μM and LC50 values ranging from 4.43 to > 100 μM. All data are compared with standard drugs fluorouracil and doxorubicin. Compound 8g showed higher potency as a cytotoxic molecule then fluorouracil. Furthermore, all new hybrids were studied for molecular docking into the active binding sites of 1HOV protein.

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Data availability

The data that support the findings of this study are available in “figshare” at https://doi.org/10.6084/m9.figshare.19367219.

References

  1. Hadiyal SD, Parmar ND, Kalavadiya PL, Lalpara JN, Joshi HS (2020) Microwave-assisted three-component domino synthesis of polysubstituted 4H-pyran derivatives and their anticancer activity. Russ J Org Chem 56:671–678

    Article  CAS  Google Scholar 

  2. Radia AJ, Lalpara JN, Modasiya IJ, Dubal GG (2021) Design and synthesis of novel 1, 3, 4-oxadiazole based azaspirocycles catalyzed by NaI under mild condition and evaluated their antidiabetic and antibacterial activities. J Heterocycl Chem 58:612–621

    Article  CAS  Google Scholar 

  3. Hadiyal SD, Lalpara JN, Parmar ND, Joshi HS (2021) Microwave irradiated targeted synthesis of pyrrolobenzodiazepine embrace 1,2,3-triazole by click chemistry synthetic aspect and evaluation of anticancer and antimicrobial activity. Polycycl Aromat Compd. https://doi.org/10.1080/10406638.2021.1913425

    Article  Google Scholar 

  4. Varmus H (2006) The new era in cancer research. Science 312:1162–1165

    Article  CAS  PubMed  Google Scholar 

  5. Hemaida AY, Hassan GS, Maarouf AR, Joubert J, El-Emam AA (2021) Synthesis and biological evaluation of thiazole-based derivatives as potential acetylcholinesterase inhibitors. ACS Omega 6:19202–19211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Santosh NM, Priyanka TS, Devanand BS (2010) Synthesis and hypolipidemic activity of novel 2-(4-(2-substituted aminothiazole-4-yl) phenoxy) acetic acid derivatives. Eur J Med Chem 45:3096–3100

    Article  Google Scholar 

  7. Ayati A, Emami S, Moghimi S, Foroumadi A (2019) Thiazole in the targeted anticancer drug discovery. Fut Med Chem 11:1929–1952

    Article  CAS  Google Scholar 

  8. Venkatachalam TK, Sudbeck EA, Mao C, Uckun FM (2001) Anti-HIV activity of aromatic and heterocyclic thiazolyl thiourea compounds. Bioorg Med Chem Lett 11:523–528

    Article  CAS  PubMed  Google Scholar 

  9. Deb PK, Kaur R, Chandrasekaran B (2014) Synthesis, anti-inflammatory evaluation, and docking studies of some new thiazole derivatives. Med Chem Res 23:2780–2792

    Article  CAS  Google Scholar 

  10. Andreani A, Rambaldi M, Locatelli A, Cristoni A, Malandrino S, Pifferi G (1992) Synthesis and antihypertensive activity of imidazo[2,1-b]-thiazoles bearing a 2,6-dichlorophenyl group. Acta Pharm Nord 4:93–96

    CAS  PubMed  Google Scholar 

  11. Sadek B, Al-Tabakha MM, Fahelelbom KM (2011) Antimicrobial prospect of newly synthesized 1,3-thiazole derivatives. Molecules 16:9386–9396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Deng XQ, Song MX, Wei CX, Li FN, Quan ZS (2010) Synthesis and anticonvulsant activity of 7-alkoxy-triazolo-[3,4-b]benzo[d]thiazoles. Med Chem 6:313–320

    Article  CAS  PubMed  Google Scholar 

  13. Singh IP, Gupta S, Kumar S (2020) Thiazole compounds as antiviral agents: an update. Med Chem 16:4–23

    Article  CAS  PubMed  Google Scholar 

  14. Kumawat MK (2018) Thiazole containing heterocycles with antimalarial activity. Curr Drug Discov Technol 15:196–200

    Article  CAS  PubMed  Google Scholar 

  15. Chirag HR, Nariya PB, Deepika M, Raghuvir RSP, Naval KP, Anilkumar SP (2021) Design, synthesis and antidiabetic activity of biphenylcarbonitrile-thiazolidinedione conjugates as potential α-amylase inhibitors. ChemistrySelect 6:2464–2469

    Article  Google Scholar 

  16. Li X, He Y, Ruiz CH, Koenig M, Cameron MD (2009) Characterization of dasatinib and its structural analogs as CYP3A4 mechanism-based inactivators and the proposed bioactivation pathways. Drug Metab Dispos 37:1242–1250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wright DG, Boosalis M, Malek K, Waraska K (2004) Effects of the IMP-dehydrogenase inhibitor, Tiazofurin, in bcr-abl positive acute myelogenous leukemia. Part II. In vitro studies. Leuk Res 28:1137–1143

    Article  CAS  PubMed  Google Scholar 

  18. Hu-Lieskovan S, Mok S, Homet Moreno B, Tsoi J, Robert L, Goedert L, Pinheiro EM, Koya RC, Graeber TG, Comin-Anduix B, Ribas A (2015) Improved antitumour activity of immunotherapy with B-RAF and MEK inhibitors in BRAF(V600E) melanoma. Sci Transl Med 7:279ra41

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kwiecień H, Goszczyńska A, Rokosz P (2016) Benzofuran small molecules as potential inhibitors of human protein kinases. A review. Curr Pharm Des 22:879–894

    Article  PubMed  Google Scholar 

  20. Napiórkowska M, Cieślak M, Kaźmierczak-Barańska J, Królewska-Golińska K, Nawrot B (2019) Synthesis of new derivatives of benzofuran as potential anticancer agents. Molecules 24:1529

    Article  PubMed  PubMed Central  Google Scholar 

  21. Khalil HS, Sedky NK, Amin KM, Abd Elhafez OM, Arafa RK (2019) Visnagin and benzofuran scaffold-based molecules as selective cyclooxygenase-2 inhibitors with anti-inflammatory and analgesic properties: design, synthesis and molecular docking. Fut Med Chem 11:659–676

    Article  CAS  Google Scholar 

  22. Jiang X, Liu W, Zhang W (2011) Synthesis and antimicrobial evaluation of new benzofuran derivatives. Eur J Med Chem 46:3526–3530

    Article  CAS  PubMed  Google Scholar 

  23. Ozlem O, Kadriye E, Cumhur K, Murat K, Misir A (2007) Characterization of a newly synthesized fluorescent benzofuran derivative and usage as a selective fiber optic sensor for Fe(III). Sens Actuators B 2:450–456

    Google Scholar 

  24. Jorg H, Steven VL, Rene S (1999) Three-step synthesis of an array of substituted benzofurans using polymer-supported reagents. J Chem Soc Perkin Trans 1(17):2421–2423

    Google Scholar 

  25. Cha-Lin K, Ji-Wang C (2001) A convenient synthesis of naturally occurring benzofuran ailanthoidol. Tetrahedron Lett 42:1111–1113

    Article  Google Scholar 

  26. Upendra S, Togati N, Arun M, Srimanta M, Debabrata M (2013) Palladium-catalyzed synthesis of benzofurans and coumarins from phenols and olefins. Angew Chem 52:12669–12673

    Article  Google Scholar 

  27. Hee-Jin H, Dong WK, Hyuk-Min K, Jin-Mi K (2018) Discovery of an orally bioavailable benzofuran analogue that serves as a β-amyloid aggregation inhibitor for the potential treatment of Alzheimer’s disease. J Med Chem 61:396–402

    Article  Google Scholar 

  28. Arias CA, Murray BE (2009) Antibiotic-resistant bugs in the 21st century–a clinical super-challenge. N Engl J Med 360(5):439–443

    Article  CAS  PubMed  Google Scholar 

  29. Feng Y, Likos JJ, Zhu L, Woodward H, Munie G, McDonald JJ, Stevens AM, Howard CP, De Crescenzo GA, Welsch D, Shieh HS, Stallings WC (2002) Solution structure and backbone dynamics of the catalytic domain of matrix metalloproteinase-2 complexed with a hydroxamic acid inhibitor. Biochim Biophys Acta 1598:10–23

    Article  CAS  PubMed  Google Scholar 

  30. Lalpara JN, Vachhani MD, Hadiyal SD, Goswami S, Dubal GG (2021) Synthesis and in vitro antidiabetic screening of novel dihydropyrimidine derivatives. Russ J Org Chem 57:241–246

    Article  CAS  Google Scholar 

  31. Lalpara JN, Hadiyal SD, Radia AJ, Dhalani JM, Dubal GG (2020) Design and Rapid Microwave Irradiated One-Pot Synthesis of Tetrahydropyrimidine Derivatives and Their Screening In Vitro Antidiabetic Activity. Polycyclic Aromat Compd. https://doi.org/10.1080/10406638.2020.1852586

    Article  Google Scholar 

  32. Naglaa FE, Marwa E, Ewies FE, Mohamed FE, Hanem MA, Marwa AF (2021) Design, synthesis, biological evaluation, and molecular docking of new benzofuran and indole derivatives as tubulin polymerization inhibitors. Drug Dev Res 83:485–500

    Google Scholar 

  33. Praveen K, Chinnappa AU, Santhosha SM, Nayak DS, SubbaRao VM, Hulikal SS, Rajeshwara A (2020) Antiproliferative potential, quantitative structure-activity relationship, cheminformatic and molecular docking analysis of quinoline and benzofuran derivatives. Eur J Chem 11:223–234

    Article  Google Scholar 

  34. Boyd MR, Paull KD (1995) Some practical considerations and application of the national cancer institute in vitro anticancer drug discovery screen. Drug Dev Res 34:91–109

    Article  CAS  Google Scholar 

  35. Shoemaker RH (2006) The NCI60 human tumor cell line anticancer drug screen. Nat Rev Cancer 6:813–823

    Article  CAS  PubMed  Google Scholar 

  36. Oleg T, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461

    Google Scholar 

  37. Mydhili G, Shalini G, Mohammad AA, Mohammad NA, Sami A, Saad A, Mazen A, Govindasamy R, Muthu T, Manju V (2021) In silico modeling and molecular docking insights of kaempferitrin for colon cancer-related molecular targets. J Saudi Chem Soc 25:101319

    Article  Google Scholar 

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Acknowledgements

The authors are grateful to the Department of Chemistry, Saurashtra University and Department of Chemistry, School of Science, RK University (Rajkot) for providing laboratory facilities. Authors also thankful to National facility for drug discovery (NFDD) for providing spectral data.

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Authors and Affiliations

  1. Department of Chemistry, Saurashtra University, Rajkot, Gujarat, 360005, India

    Sanjay D. Hadiyal & H. S. Joshi

  2. Department of Chemistry, RK University, Rajkot, Gujarat, 360020, India

    Sanjay D. Hadiyal, Jaydeep N. Lalpara & Bhavin B. Dhaduk

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  1. Sanjay D. Hadiyal
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  2. Jaydeep N. Lalpara
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  4. H. S. Joshi
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Correspondence to H. S. Joshi.

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Hadiyal, S.D., Lalpara, J.N., Dhaduk, B.B. et al. Rational synthesis, anticancer activity, and molecular docking studies of novel benzofuran liked thiazole hybrids. Mol Divers 27, 1345–1357 (2023). https://doi.org/10.1007/s11030-022-10493-7

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