Design, synthesis of benzimidazole tethered 3,4-dihydro-2H-benzo[e] [1, 3] oxazines as anticancer agents
Molecular Diversity - Trang 1-15 - 2023
Tóm tắt
A series of novel 3-(1H-benzo[d]imidazol-2-yl)-3,4-dihydro-2H-benzo[e][1,3] oxazine analogues synthesized through a two-step synthetic protocol. The structure of the compounds were established by interpretation 1H NMR, 13C NMR and Mass spectral data recorded after purification. All the title compounds 4a–k were screened for their in vitro anti-cancer activity against two breast cancer cell lines MCF 7 and MDA-MB-231 by using Doxorubicin as standard reference. Compound 4e displayed superior activity against both the cell lines MCF-7 and MDA-MB-231 with IC50 values of 8.60 ± 0.75 and 6.30 ± 0.54 µM respectively, compared to the Doxorubicin IC50 value of 9.11 ± 0.54 and 8.47 ± 0.47 µM. Compound 4i also indicated good activity with IC50 value of 9.85 ± 0.69 μM on par with Doxorubicin against MCF-7 cells. Compound 4g demonstrated best activity on par with standard reference to IC50 value of 8.52 ± 0.62 μM against MDA-MB-231 cell line. And all other compounds demonstrated good to moderate activity compared to Doxorubicin. Docking studies against EGFR showed that all the compounds have very good binding affinities towards the target. The predicted drug-likeness properties of all compounds enable them to be used as therapeutic agents.
Tài liệu tham khảo
Al-Ghorbani M, Bushra Begum A, Zabiulla Z et al (2015) Piperazine and morpholine: synthetic preview and pharmaceutical applications. Res J Pharm Technol 8:611–628. https://doi.org/10.5958/0974-360X.2015.00100.6
Sawyer TK (2007) Novel Small-Molecule Inhibitors of Src Kinase for Cancer Therapy. Cancer. https://doi.org/10.1007/7355_2006_010
Mathur G, Nain S, Sharma PK (2015) Cancer: an overview. Acad J Cancer Res 8(1):1–9
Hassanpour SH, Dehghani M (2017) Review of cancer from perspective of molecular. J Cancer Res Pract 4:127–129. https://doi.org/10.1016/j.jcrpr.2017.07.001
Mallikanti V, Thumma V, Veeranki KC et al (2022) Synthesis, cytotoxicity, molecular docking and ADME assay of novel morpholine appended 1,2,3-triazole analogues. ChemistrySelect 7:e202204020. https://doi.org/10.1002/slct.202204020
Ruddarraju RR, Murugulla AC, Kotla R et al (2017) Design, synthesis, anticancer activity and docking studies of theophylline containing 1,2,3-triazoles with variant amide derivatives. Medchemcomm 8:176–183. https://doi.org/10.1039/C6MD00479B
Sun C, Chen C, Xu S et al (2016) Synthesis and anticancer activity of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety. Bioorg Med Chem 24:3862–3869. https://doi.org/10.1016/j.bmc.2016.06.032
Organization WH Cancer. http://www.who.int/cancer/en/. Accessed 9 Oct 2018
Lee CY, Chew EH, Go ML (2010) Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR. Eur J Med Chem 45:2957–2971. https://doi.org/10.1016/j.ejmech.2010.03.023
Vásquez D, Rodríguez JA, Theoduloz C et al (2010) Studies on quinones. Part 46. Synthesis and in vitro antitumor evaluation of aminopyrimidoisoquinolinequinones. Eur J Med Chem 45:5234–5242. https://doi.org/10.1016/j.ejmech.2010.08.040
Arcamone F, Cassinelli G, Fantini G et al (1969) Adriamycin, 14-hydroxydaimomycin, a new antitumor antibiotic from S Peucetius var caesius. Biotechnol Bioeng 11:1101–1110. https://doi.org/10.1002/bit.260110607
Cortés-Funes H, Coronado C (2007) Role of anthracyclines in the era of targeted therapy. Cardiovasc Toxicol 7:56–60. https://doi.org/10.1007/s12012-007-0015-3
Robledo-Cadena DX, Gallardo-Pérez JC, Dávila-Borja V et al (2020) Non-steroidal anti-inflammatory drugs increase cisplatin, paclitaxel, and doxorubicin efficacy against human cervix cancer cells. Pharmaceuticals 13:1–25. https://doi.org/10.3390/ph13120463
Rushing DA, Raber SR, Rodvold KA et al (1994) The effects of cyclosporine on the pharmacokinetics of doxorubicin in patients with small cell lung cancer. Cancer 74:834–841
van der Zanden SY, Qiao X, Neefjes J (2021) New insights into the activities and toxicities of the old anticancer drug doxorubicin. FEBS J 288:6095–6111. https://doi.org/10.1111/febs.15583
Shukla A, Hillegass JM, MacPherson MB et al (2010) Blocking of ERK1 and ERK2 sensitizes human mesothelioma cells to doxorubicin. Mol Cancer 9:1–13. https://doi.org/10.1186/1476-4598-9-314
Byron SA, Loch DC, Pollock PM (2012) Fibroblast growth factor receptor inhibition synergizes with paclitaxel and doxorubicin in endometrial cancer cells. Int J Gynecol Cancer 22:1517–1526. https://doi.org/10.1097/IGC.0b013e31826f6806
Sergei B, Pavel D, Aigul G et al (2020) Inhibition of FGFR2-signaling attenuates a homology-mediated dna repair in gist and sensitizes them to DNA-topoisomerase II inhibitors. Int J Mol Sci 21:352. https://doi.org/10.3390/ijms21010352
Swain SM, Whaley FS, Ewer MS (2003) Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97:2869–2879. https://doi.org/10.1002/cncr.11407
Vishnu T, Veerabhadraiah M, Krishna Chaitanya V et al (2022) Design, synthesis and anticancer activity of 5-((2-(4-bromo/chloro benzoyl) benzofuran-5-yl) methyl)-2-((1-(substituted)-1H-1,2,3-triazol-4-yl)methoxy)benzaldehyde analogues. Mol Divers. https://doi.org/10.1007/s11030-022-10575-6
Vasava MS, Bhoi MN, Rathwa SK et al (2020) Benzimidazole: a milestone in the field of medicinal chemistry. Mini Rev Med Chem 20:532–565
Pérez-Villanueva J, Santos R, Hernández-Campos A et al (2011) Structure–activity relationships of benzimidazole derivatives as antiparasitic agents: Dual activity-difference (DAD) maps. Med Chem Commun 2:44–49. https://doi.org/10.1039/C0MD00159G
Shingalapur RV, Hosamani KM, Keri RS, Hugar MH (2010) Derivatives of benzimidazole pharmacophore: Synthesis, anticonvulsant, antidiabetic and DNA cleavage studies. Eur J Med Chem 45:1753–1759. https://doi.org/10.1016/j.ejmech.2010.01.007
Siddiqui N, Alam MS, Sahu M et al (2016) Antidepressant, analgesic activity and SAR studies of substituted benzimidazoles. Asian J Pharm Res 6:170. https://doi.org/10.5958/2231-5691.2016.00024.1
Wang XJ, Xi MY, Fu JH et al (2012) Synthesis, biological evaluation and SAR studies of benzimidazole derivatives as H1-antihistamine agents. Chin Chem Lett 23:707–710. https://doi.org/10.1016/j.cclet.2012.04.020
Ganie AM, Dar AM, Khan FA, Dar BA (2019) Benzimidazole derivatives as potential antimicrobial and antiulcer agents: a mini review. Mini-Rev Med Chem 19:1292–1297. https://doi.org/10.2174/1381612824666181017102930
Jain A, Sharma R, Chaturvedi SC (2013) A rational design, synthesis, characterization, and antihypertensive activities of some new substituted benzimidazoles. Med Chem Res 22:4622–4632. https://doi.org/10.1007/s00044-012-0462-7
Kanwal A, Ahmad M, Aslam S et al (2019) Recent advances in antiviral benzimidazole derivatives: a mini review. Pharm Chem J 53:179–187. https://doi.org/10.1007/s11094-019-01976-3
Othman DIA, Hamdi A, Tawfik SS et al (2023) Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition, in vitro and in silico studies. J Enzyme Inhib Med Chem 38:2166037
Ouahrouch A, Ighachane H, Taourirte M et al (2014) Benzimidazole-1,2,3-triazole hybrid molecules: synthesis and evaluation for antibacterial/antifungal activity. Arch Pharm (Weinheim) 347:748–755. https://doi.org/10.1002/ardp.201400142
Bansal Y, Silakari O (2014) Synthesis and pharmacological evaluation of polyfunctional benzimidazole-NSAID chimeric molecules combining anti-inflammatory, immunomodulatory and antioxidant activities. Arch Pharm Res 37:1426–1436
Syed A, Syeda A (2008) Spectrophotometric determination of certain benzimidazole proton pump inhibitors. Indian J Pharm Sci 70:507. https://doi.org/10.4103/0250-474X.44605
Pathare B, Bansode T (2021) Review- biological active benzimidazole derivatives. Results Chem 3:100200. https://doi.org/10.1016/j.rechem.2021.100200
Law CSW, Yeong KY (2021) Benzimidazoles in Drug Discovery: A Patent Review. ChemMedChem 16:1861–1877. https://doi.org/10.1002/cmdc.202100004
Ren Y, Wang Y, Li G et al (2021) Discovery of Novel Benzimidazole and Indazole Analogues as Tubulin Polymerization Inhibitors with Potent Anticancer Activities. J Med Chem 64:4498–4515. https://doi.org/10.1021/acs.jmedchem.0c01837
Akhtar MdJ, Yar MS, Sharma VK et al (2020) Recent Progress of Benzimidazole Hybrids for Anticancer Potential. Curr Med Chem 27:5970–6014. https://doi.org/10.2174/0929867326666190808122929
Wu K, Peng X, Chen M et al (2022) Recent progress of research on anti-tumor agents using benzimidazole as the structure unit. Chem Biol Drug Des 99:736–757. https://doi.org/10.1111/cbdd.14022
Ali AM, Tawfik SS, Mostafa AS, Massoud MAM (2022) Benzimidazole-based protein kinase inhibitors: Current perspectives in targeted cancer therapy. Chem Biol Drug Des 100:656–673. https://doi.org/10.1111/cbdd.14130
Tan YJ, Lee YT, Yeong KY et al (2018) Anticancer activities of a benzimidazole compound through sirtuin inhibition in colorectal cancer. Future Med Chem 10:2039–2057. https://doi.org/10.4155/fmc-2018-0052
Coleman RL, Fleming GF, Brady MF et al (2019) Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med 381:2403–2415. https://doi.org/10.1056/NEJMoa1909707
Chen J, Li N, Liu B et al (2020) Pracinostat (SB939), a histone deacetylase inhibitor, suppresses breast cancer metastasis and growth by inactivating the IL-6/STAT3 signalling pathways. Life Sci 248:117469. https://doi.org/10.1016/j.lfs.2020.117469
Barman Balfour JA, Goa KL (2001) Bendamustine. Drugs 61:631–638. https://doi.org/10.2165/00003495-200161050-00009
Markham A, Keam SJ (2020) Selumetinib: first approval. Drugs 80:931–937. https://doi.org/10.1007/s40265-020-01331-x
Woodfield SE, Zhang L, Scorsone KA et al (2016) Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression. BMC Cancer 16:172. https://doi.org/10.1186/s12885-016-2199-z
Bryson HM, Wagstaff AJ (1996) Liarozole. Drugs Aging 9:478–484. https://doi.org/10.2165/00002512-199609060-00010
Akhter M, Habibullah S, Hasan SM et al (2011) Synthesis of some new 3,4-dihydro-2H-1,3-benzoxazines under microwave irradiation in solvent-free conditions and their biological activity. Med Chem Res 20:1147–1153. https://doi.org/10.1007/s00044-010-9451-x
Kakkerla R, Marri S, Krishna MPSM et al (2018) Synthesis and biological evaluation of 3,4-dihydro-3-(3-methylisoxazol-5- yl)-2H-benzo[e] [1,3] oxazine derivatives as anticancer agents. Lett Org Chem. https://doi.org/10.2174/1570178614666170623121207
Mathew BP, Kumar A, Sharma S et al (2010) An eco-friendly synthesis and antimicrobial activities of dihydro-2H-benzo- and naphtho-1,3-oxazine derivatives. Eur J Med Chem 45:1502–1507. https://doi.org/10.1016/j.ejmech.2009.12.058
Kategaonkar AH, Sonar SS, Pokalwar RU et al (2010) An efficient synthesis of 3,4-dihydro-3-substituted-2H-naphtho[2,1-e] [1,3]o xazine derivatives catalyzed by zirconyl(IV) chloride and evaluation of its biological activities. Bull Korean Chem Soc 31:1657–1660. https://doi.org/10.5012/bkcs.2010.31.6.1657
Kang Y-G, Park C-Y, Shin H et al (2015) Synthesis and anti-tubercular activity of 2-nitroimidazooxazines with modification at the C-7 position as PA-824 analogs. Bioorg Med Chem Lett 25:3650–3653. https://doi.org/10.1016/j.bmcl.2015.06.060
Zhang H-J, Li Y-F, Cao Q et al (2017) Pharmacological evaluation of 9,10-dihydrochromeno[8,7-e] [1,3] oxazin-2(8H)-one derivatives as potent anti-inflammatory agent. Pharmacol Rep 69:419–425. https://doi.org/10.1016/j.pharep.2016.12.006
Chen C-L, Lee C-C, Liu F-L et al (2016) Design, synthesis and SARs of novel salicylanilides as potent inhibitors of RANKL-induced osteoclastogenesis and bone resorption. Eur J Med Chem 117:70–84. https://doi.org/10.1016/j.ejmech.2016.04.007
Gawali R, Trivedi J, Bhansali S et al (2018) Design, synthesis, docking studies and biological screening of 2-thiazolyl substituted -2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines as potent HIV-1 reverse transcriptase inhibitors. Eur J Med Chem 157:310–319. https://doi.org/10.1016/j.ejmech.2018.07.067
Ho Y-J, Lu J-W, Ho L-J et al (2019) Anti-inflammatory and anti-osteoarthritis effects of Cm-02 and Ck-02. Biochem Biophys Res Commun 517:155–163. https://doi.org/10.1016/j.bbrc.2019.07.036
Ihmaid S, Al-Rawi J, Bradley C et al (2011) Synthesis, structural elucidation, DNA-PK inhibition, homology modelling and anti-platelet activity of morpholino-substituted-1,3-naphth-oxazines. Bioorg Med Chem 19:3983–3994. https://doi.org/10.1016/j.bmc.2011.05.032
Viegas-Junior C, Danuello A, da Silva BV et al (2007) Molecular hybridization: a useful tool in the design of new drug prototypes. Curr Med Chem 14:1829–1852
Ivasiv V, Albertini C, Gonçalves AE et al (2019) Molecular hybridization as a tool for designing multitarget drug candidates for complex diseases. Curr Top Med Chem 19:1694–1711
Fraga CAM (2009) Drug hybridization strategies: before or after lead identification? Expert Opin Drug Discov 4:605–609
Nagamani M, Vishnu T, Jalapathi P, Srinivas M (2022) Molecular docking studies on COVID-19 and antibacterial evaluation of newly synthesized 4-(methoxymethyl)-1,2,3-triazolean analogues derived from (E)-1-phenyl-3-(2-(piperidin-1-yl)quinolin-3-yl) prop-2-en-1-one. J Iran Chem Soc 19:1049–1060. https://doi.org/10.1007/s13738-021-02365-y
Veeranna D, Ramdas L, Ravi G et al (2022) Synthesis of 1,2,3-triazole tethered indole derivatives: evaluation of anticancer activity and molecular docking studies. ChemistrySelect 7:e202201758. https://doi.org/10.1002/slct.202201758
Liu Z, Liu Y, Zeng G et al (2018) Application of molecular docking for the degradation of organic pollutants in the environmental remediation: a review. Chemosphere 203:139–150. https://doi.org/10.1016/j.chemosphere.2018.03.179
Morris GM, Ruth H, Lindstrom W et al (2009) Software news and updates AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30:2785–2791. https://doi.org/10.1002/jcc.21256
Trott O, Olson AJ (2009) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem NA-NA. https://doi.org/10.1002/jcc.21334
Friesner RA, Banks JL, Murphy RB et al (2004) Glide: a new approach for rapid, accurate docking and scoring. 1. method and assessment of docking accuracy. J Med Chem 47:1739–1749. https://doi.org/10.1021/jm0306430
Dallakyan S, Olson AJ (2015) Small-molecule library screening by docking with PyRx. In: Hempel JE, Williams CH, Hong CC (eds) Methods in Molecular Biology. Springer, pp 243–250
Verdonk ML, Cole JC, Hartshorn MJ et al (2003) Improved protein-ligand docking using GOLD. Prot: Struct Funct Bioinform 52:609–623. https://doi.org/10.1002/prot.10465
Rarey M, Kramer B, Lengauer T, Klebe G (1996) A fast flexible docking method using an incremental construction algorithm. J Mol Biol 261:470–489. https://doi.org/10.1006/jmbi.1996.0477
Bitencourt-Ferreira G, de Azevedo WF (2019) Molegro Virtual Docker for Docking. In: Filgueira W, de Azevedo, (eds) Docking screens for drug discovery. Springer, New York
Acharya R, Chacko S, Bose P et al (2019) Structure based multitargeted molecular docking analysis of selected furanocoumarins against breast cancer. Sci Rep 9:15743. https://doi.org/10.1038/s41598-019-52162-0
Yun C-H, Boggon TJ, Li Y et al (2007) Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell 11:217–227. https://doi.org/10.1016/j.ccr.2006.12.017
Seshacharyulu P, Ponnusamy MP, Haridas D et al (2012) Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets 16:15–31. https://doi.org/10.1517/14728222.2011.648617
Perike N, Edigi PK, Nirmala G, et al (2022) Synthesis, Anticancer Activity and Molecular Docking Studies of Hybrid Molecules Containing Indole-Thiazolidinedione-Triazole Moieties. ChemistrySelect. https://doi.org/10.1002/slct.202203778
Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7:1–13
Martin YC (2005) A bioavailability score. J Med Chem 48:3164–3170. https://doi.org/10.1021/jm0492002
Lipinski CA (2004) Lead-and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 1:337–341
Ertl P, Schuffenhauer A (2009) Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions. J Cheminform 1:1–11
Sabhavath AK, Madderla S, Dharavath R et al (2022) Synthesis of 1,2,3-triazole-containing 2,3-dihydrofuran derivatives, evaluation of anticancer activity and molecular docking studies. ChemistrySelect 7:e202203847. https://doi.org/10.1002/slct.202203847
Ashok D, Thara G, Kumar BK et al (2023) Microwave-assisted synthesis, molecular docking studies of 1,2,3-triazole-based carbazole derivatives as antimicrobial, antioxidant and anticancer agents. RSC Adv 13:25–40. https://doi.org/10.1039/D2RA05960F