Login Register Cart 0
Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis and Anticancer Activity of Novel Chromene Derivatives, Chromeno[2,3-d][1,3]Oxazines, and Chromeno[2,3-d]Pyrimidines

Author(s): Mahmoud N.M. Yousif*, Usama Fathy and Nabil M. Yousif

Volume 19, Issue 6, 2023

Published on: 13 January, 2023

Page: [578 - 585] Pages: 8

DOI: 10.2174/1573406419666221226094133

Price: $65

Abstract

Background: Several chromene derivatives have a wide variety of biological and pharmacological activity. They had anticancer activity, antimicrobial activity, antituberculosis activity, anticonvulsant activity, antidiabetic activity, antichlolinesterase activity, and inhibitor of monoamine oxidase activity. The above-mentioned activities directed us to synthesize novel chromene derivatives, chromeno[2,3-d][1,3]oxazines, and chromeno[2,3-d]pyrimidines. The starting material was 2- amino-8-(2-chlorobenzylidene)-4-(2-chlorophenyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile.

Methods: Several novel chromene derivatives had been synthesized. Compound 1 reacted with carbon disulfide, and ethyl chloroformate to afford chromene derivatives 2, 3. Chromene derivative 3 reacted with hydrazine dydrate to give compound 4. Chromene derivative 1 reacted with acetic acid and sulphuric acid to produce compounds 5, and 6. Amino derivative 5 reacted with chloroacyl derivative to afford compounds 7a-c which cycalized in dry xylene to afford compounds 8a-c. Chromene derivative 8a reacted with hydroxyl amine to afford compound 9.

Results: The structures of novel synthesized chromene derivatives had been confirmed using mass spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and elemental analysis. Most of the prepared compounds were screened against liver cancer cell lines (HepG-2), human colon cancer cell lines (HT-29), and breast adenocarcinoma cell lines (MCF-7). Chromene derivative 2 had anticancer activity against human colon cancer cell lines (HT-29) higher than the reference drug doxorubicin. The rest of the tested compounds had anticancer activity against human colon cancer cell lines (HT-29) lower than that of the reference drug doxorubicin. Chromene derivative 5 had anticancer activity against liver cancer cell lines (HepG-2) higher than the reference drug doxorubicin.

Conclusion: Several chromene derivatives had been synthesized and their structures had been confirmed using different spectroscopic techniques. Some of the chromene derivatives that were screened against different cancer cell lines showed promising anticancer activity higher than the reference standard drug. For example, chromene derivative 2 had anticancer activity against human colon cancer cell lines (HT-29) higher than the reference drug doxorubicin. Chromene derivative 5 had anticancer activity against liver cancer cell lines (HepG-2) higher than the reference drug doxorubicin. Chromene derivative 6 had anticancer activity against breast adenocarcinoma cell lines (MCF-7) higher than the standard drug.

Keywords: Anticancer activity, chromene, chromeno[2, 3-d][1, 3]oxazines, 3-d]pyrimidines, oxazines, synthesis.

« Previous Next »
Graphical Abstract

[1]
Eisnor, C.R.; Gossage, R.A.; Yadav, P.N. Oxazoline Chemistry. Part 11: Syntheses of natural and synthetic isoflavones, stilbenes and related species via C–C bond formation promoted by a Pd–oxazoline complex. Tetrahedron, 2006, 62(14), 3395-3401.
[http://dx.doi.org/10.1016/j.tet.2006.01.046]
[2]
Raj, V.; Lee, J. 2H/4H-Chromenes-A Versatile Biologically Attractive Scaffold. Front Chem., 2020, 8, 623-646.
[http://dx.doi.org/10.3389/fchem.2020.00623] [PMID: 32850645]
[3]
Abd-El-Aziz, A.S.; El-Ghezlani, E.G.; Elaasser, M.M.; Afifi, T.H.; Okasha, R.M. First example of cationic cyclopentadienyliron based chromene complexes and polymers: Synthesis, characterization, and biological applications. J. Inorg. Organomet. Polym. Mater., 2020, 30(1), 131-146.
[http://dx.doi.org/10.1007/s10904-019-01295-w]
[4]
Afifi, T.H.; Riyadh, S.M.; Deawaly, A.A.; Naqvi, A. Novel chromenes and benzochromenes bearing arylazo moiety: Molecular docking, in-silico admet, in-vitro antimicrobial and anticancer screening. Med. Chem. Res.,, 2019, 28(9), 1471-1487.
[http://dx.doi.org/10.1007/s00044-019-02387-5]
[5]
Ahmed, H.E.A.; El-Nassag, M.A.A.; Hassan, A.H.; Mohamed, H.M. Halawa, A.H.; Okasha, R.M.; Ihmaid, S.; Abd El-Gilil, S.M.; Khattab, E.S.A.E.H.; Fouda, A.M.; El-Agrody, A.M.; Aljuhani, A.; Afifi, T.H. Developing lipophilic aromatic halogenated fused systems with specific ring orientations, leading to potent anticancer analogs and targeting the c-Src Kinase enzyme. J. Mol. Struct.,, 2019, 1186, 212-223.
[http://dx.doi.org/10.1016/j.molstruc.2019.03.012]
[6]
Takao, K.U, S.; Kamauchi, H.; Sugita, Y. Design, synthesis and evaluation of 2-(indolylmethylidene)-2,3-dihydro-1-benzofuran-3-one and 2-(indolyl)-4H-chromen-4-one derivatives as novel monoamine oxidases inhibitors. Bioorg. Chem., 2019, 87, 594-600.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.042] [PMID: 30933784]
[7]
Rawat, P.; Verma, S.M. Design and synthesis of chroman derivatives with dual anti-breast cancer and antiepileptic activities. Drug Des. Devel. Ther., 2016, 10, 2779-2788.
[http://dx.doi.org/10.2147/DDDT.S111266] [PMID: 27621598]
[8]
Suvarna, V.; Murahari, M.; Khan, T.; Chaubey, P.; Sangave, P. Phytochemicals and PI3K inhibitors in cancer-an insight. Front. Pharmacol., 2017, 8, 916.
[http://dx.doi.org/10.3389/fphar.2017.00916] [PMID: 29311925]
[9]
Mashhadinezhad, M.; Mamaghani, M.; Rassa, M.; Shirini, F. A facile green synthesis of chromene derivatives as antioxidant and antibacterial agents through a modified natural soil. ChemistrySelect, 2019, 4(17), 4920-4932.
[http://dx.doi.org/10.1002/slct.201900405]
[10]
Tehrani, M.B.; Rezaei, Z.; Asadi, M.; Behnammanesh, H.; Nadri, H.; Afsharirad, F.; Moradi, A.; Larijani, B.; Mohammadi-Khanaposhtani, M.; Mahdavi, M. Design, synthesis, and cholinesterase inhibition assay of coumarin-3-carboxamide-n-morpholine hybrids as new anti-Alzheimer agents. Chem. Biodivers., 2019, 16(7), e1900144.
[http://dx.doi.org/10.1002/cbdv.201900144] [PMID: 31155827]
[11]
Ahmed, M.N.; Ghias, M.; Shah, S.W.A.; Shoaib, M.; Tahir, M.N.; Ashfaq, M.; Ibrahim, M.A.A.; Andleeb, H.; Gil, D.M.; Frontera, A. X-ray characterization, Hirshfeld surface analysis, DFT calculations, in vitro and in silico lipoxygenase inhibition (LOX) studies of dichlorophenyl substituted 3-hydroxy-chromenones. New J. Chem., 2021, 45(42), 19928-19940.
[http://dx.doi.org/10.1039/D1NJ04340D]
[12]
Vosooghi, M.; Rajabalian, S.; Sorkhi, M.; Badinloo, M.; Nakhjiri, M.; Negahbani, A.S.; Asadipour, A.; Mahdavi, M.; Shafiee, A.; Foroumadi, A. Synthesis and cytotoxic activity of some 2-amino-4-aryl-3-cyano-7-(dimethylamino)-4H-chromenes. Res. Pharm. Sci., 2010, 5(1), 9-14.
[PMID: 21589763]
[13]
Choi, M.; Hwang, Y.S.; Kumar, A.S.; Jo, H.; Jeong, Y.; Oh, Y.; Lee, J.; Yun, J.; Kim, Y.; Han, S.; Jung, J.K.; Cho, J.; Lee, H. Design and synthesis of 3,4-dihydro-2H-benzo[h]chromene derivatives as potential NF-κB inhibitors. Bioorg. Med. Chem. Lett., 2014, 24(11), 2404-2407.
[http://dx.doi.org/10.1016/j.bmcl.2014.04.053] [PMID: 24792464]
[14]
Angelova, V.T.; Andreeva-Gateva, P.A.; Vassilev, N.G.; Tafradjiiska-Hadjiolova, R.; Surcheva, S.; Tchekalarova, J. Anticonvulsant activity of newly synthesized 2H-chromene based hydrazones in ICR mice. Comp. Rend. Acad. Bulg. Sci., 2016, 69, 513-520.
[15]
Kale, A.; Bingi, C.; Sripada, S.; Ganesh Kumar, C.; Atmakur, K. A simple, one pot synthesis of furo[3,2- c]chromenes and evaluation of antimicrobial activity. Bioorg. Med. Chem. Lett., 2016, 26(20), 4899-4902.
[http://dx.doi.org/10.1016/j.bmcl.2016.09.022] [PMID: 27641471]
[16]
Saeedi, M.; Safavi, M.; Karimpour-Razkenari, E.; Mahdavi, M.; Edraki, N.; Moghadam, F.H.; Khanavi, M.; Akbarzadeh, T. Synthesis of novel chromenones linked to 1,2,3-triazole ring system: Investigation of biological activities against Alzheimer’s disease. Bioorg. Chem., 2017, 70, 86-93.
[http://dx.doi.org/10.1016/j.bioorg.2016.11.011] [PMID: 27914694]
[17]
Spasov, A.A.; Babkov, D.A.; Osipov, D.V.; Klochkov, V.G.; Prilepskaya, D.R.; Demidov, M.R.; Osyanin, V.A.; Klimochkin, Y.N. Synthesis, in vitro and in vivo evaluation of 2-aryl-4H-chromene and 3-aryl-1H-benzo[f]chromene derivatives as novel α-glucosidase inhibitors. Bioorg. Med. Chem. Lett., 2019, 29(1), 119-123.
[http://dx.doi.org/10.1016/j.bmcl.2018.10.018] [PMID: 30340897]
[18]
Zhao, W.; Wang, B.; Liu, Y.; Fu, L.; Sheng, L.; Zhao, H.; Lu, Y.; Zhang, D. Design, synthesis, and biological evaluation of novel 4H-chromen-4-one derivatives as antituberculosis agents against multidrug-resistant tuberculosis. Eur. J. Med. Chem., 2020, 189, 112075.
[http://dx.doi.org/10.1016/j.ejmech.2020.112075] [PMID: 31986405]
[19]
Ali, A.; Khalid, M.; Tahir, M.N.; Imran, M.; Ashfaq, M.; Hussain, R.; Assiri, M.A.; Khan, I. Synthesis of diaminopyrimidine sulfonate derivatives and exploration of their structural and quantum chemical insights via SC-XRD and the DFT Approach. ACS Omega, 2021, 6(10), 7047-7057.
[http://dx.doi.org/10.1021/acsomega.0c06323] [PMID: 33748618]
[20]
Ali, A.; Khalid, M.; Rehman, M.F.; Haq, S.; Ali, A.; Tahir, M.N.; Ashfaq, M.; Rasool, F.; Braga, A.A.C. Efficient synthesis, SC-XRD, and theoretical studies of O -benzenesulfonylated pyrimidines: Role of noncovalent interaction influence in their supramolecular network. ACS Omega, 2020, 5(25), 15115-15128.
[http://dx.doi.org/10.1021/acsomega.0c00975] [PMID: 32637784]
[21]
Tahir, M.N.; Ashfaq, M.; de la Torre, A.F.; Caballero, J.; Hernández-Rodríguez, E.W.; Ali, A. Rationalizing the stability and interactions of 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium 2-hydroxy-3,5-dinitrobenzoate salt. J. Mol. Struct., 2019, 1193, 185-194.
[http://dx.doi.org/10.1016/j.molstruc.2019.05.003]
[22]
Ashfaq, M.; Tahir, M.N.; Kuznetsov, A.; Mirza, S.H.; Khalid, M.; Ali, A. DFT and single crystal analysis of the pyrimethamine-based novel co-crystal salt: 2,4-Diamino-5-(4-chloro-phenyl)-6-ethylpyrimidin-1-ium:4-Hydroxybenzoate:Methanol:Hydrate (1:1:1:1) (DEHMH). J. Mol. Struct., 2020, 1199, 127041-127050.
[http://dx.doi.org/10.1016/j.molstruc.2019.127041]
[23]
Ashfaq, M.; Bogdanov, G.; Glebov, V.; Ali, A.; Tahir, M.N.; Abdullah, S. Single crystal investigation, Hirshfeld surface analysis and DFT exploration of the pyrimethamine-based novel organic salt: 2, 4-Diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium 3-carboxybenzoate hydrate (1:1:1). J. Mol. Struct., 2021, 1224, 129309-129317.
[http://dx.doi.org/10.1016/j.molstruc.2020.129309]
[24]
Khalid, M.; Ali, A.; Haq, S.; Tahir, M.N.; Iqbal, J.; Braga, A.A.C.; Ashfaq, M.; Akhtar, S.U.H. O-4-Acetylamino-benzenesulfonylated pyrimidine derivatives: Synthesis, SC-XRD, DFT analysis and electronic behaviour investigation. J. Mol. Struct., 2021, 1224, 129308-129318.
[http://dx.doi.org/10.1016/j.molstruc.2020.129308]
[25]
Ashfaq, M.; Ali, A.; Kuznetsov, A.; Tahir, M.N.; Khalid, M. DFT and single-crystal investigation of the pyrimethamine-based novel co-crystal salt: 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium-4-methylbenzoate hydrate (1:1:1) (DEMH). J. Mol. Struct., 2021, 1228, 129445.
[http://dx.doi.org/10.1016/j.molstruc.2020.129445]
[26]
Ashfaq, M.; Bogdanov, G.; Ali, A.; Tahir, M.N.; Abdullah, S. Pyrimethamine-based novel co-crystal salt: Synthesis, single-crystal investigation, Hirshfeld surface analysis and DFT inspection of the 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium 2,4-dichlorobenzoate (1:1) (DECB). J. Mol. Struct., 2021, 1235, 130215-130221.
[http://dx.doi.org/10.1016/j.molstruc.2021.130215]
[27]
Ali, A.; Kuznetsov, A.; Ashfaq, M.; Tahir, M.N.; Khalid, M.; Imran, M.; Irfan, A. Synthesis, single-crystal exploration, and theoretical insights of arylsulfonylated 2-amino-6-methylpyrimidin derivatives. J. Mol. Struct., 2021, 1243, 130789-130804.
[http://dx.doi.org/10.1016/j.molstruc.2021.130789]
[28]
Jalili, B.; Ghafoori, H.; Jalili, P. Investigation of carbon nano-tube (CNT) particles effect on the performance of a refrigeration cycle. Int. J. Mater. Sci. Innov., 2014, 2(1), 8-17.
[29]
Jalili, B.; Aghaee, N.; Jalili, P.; Domiri Ganji, D. Novel usage of the curved rectangular fin on the heat transfer of a double-pipe heat exchanger with a nanofluid. Case Stud. Therm. Eng., 2022, 35, 102086.
[http://dx.doi.org/10.1016/j.csite.2022.102086]
[30]
Jalili, P.; Kazerani, K.; Jalili, B.; Ganji, D.D. Investigation of thermal analysis and pressure drop in non-continuous helical baffle with different helix angles and hybrid nano-particles. Case Stud. Therm. Eng., 2022, 36, 102209.
[http://dx.doi.org/10.1016/j.csite.2022.102209]
[31]
Jalili, B.; Sadighi, S.; Jalili, P.; Ganji, D.D. Numerical analysis of MHD nanofluid flow and heat transfer in a circular porous medium containing a Cassini oval under the influence of the Lorentz and buoyancy forces. Heat Transf., 2022, 51(7), 6122-6138.
[http://dx.doi.org/10.1002/htj.22582]
[32]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]

Rights & Permissions Print Cite
Article Metrics
43
1
© 2024 Bentham Science Publishers | Privacy Policy