Login Register Cart 0
Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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

Chromenes - A Novel Class of Heterocyclic Compounds: Recent Advancements and Future Directions

Author(s): Anurag Chaudhary*, Kalpana Singh, Nishant Verma, Sachin Kumar, Deepak Kumar and Prince Prashant Sharma

Volume 22, Issue 21, 2022

Published on: 25 May, 2022

Page: [2736 - 2751] Pages: 16

DOI: 10.2174/1389557522666220331161636

Price: $65

Abstract

Chromenes are an important class of oxygen-containing heterocyclic compounds with intriguing biological activity, a simple structure with mild adverse effects. Chromenes are abundantly found in nature in the form of alkaloids, tocopherols, flavone, and anthocyanins. The Chromene nucleus is an important moiety for the discovery of new drug candidates. Chromene derivatives have shown various pharmacological activities like antiviral, anticancer, anti-inflammatory, antitumour, antimicrobial, antiproliferative, anticholinesterase, EPR-1 (Effector cell Protease Receptor-1) antagonist and MAO (Mono-Amine Oxidase) inhibitors. In SAR (Structure Activity Relationship) studies with chromene nucleus, it was found that 4-aryl moiety, 3-cyano group, and 2-amino group are essential for the cytotoxic activity. Substitution at the 7th position with electron donating group enhances the pharmacological activity whereas the electron withdrawing group decreases the pharmacological activity. Structural modifications at the chromene ring, middle aliphatic portion, and terminal aromatic ring yielded more potential 5-HT1A (5-Hydroxytryptamine 1A) receptor affinity and antidiabetic activity. Chromenes with cyclic secondary amine and 4-hydroxy phenyl substituents yielded potent antimicrobial compounds. This review summarizes the importance of chromenes in rational drug design and the development of novel molecules with a variety of pharmacological activities.

Keywords: Chromenes, heterocyclic compounds, anticancer, antidiabetic, antimicrobial, pharmacological activities.

« Previous Next »
Graphical Abstract

[1]
Ren, Q.; Siau, W.Y.; Du, Z.; Zhang, K.; Wang, J. Expeditious assembly of a 2-amino-4H-chromene skeleton by using an enantioselective Mannich intramolecular ring cyclization-tautomerization cascade sequence. Chemistry, 2011, 17(28), 7781-7785.
[http://dx.doi.org/10.1002/chem.201100927] [PMID: 21618299]
[2]
Hussain, M.K.; Khan, M.F.; Khatoon, S.; Al-Sehemi, A.G.; Saquib, M. Chromenes: Phytomolecules with immense therapeutic potential. In: Swami, M.K., Ed.; Plant-derived Bioactives: Chemistry and Mode of Action; Springer Nature: Singapore, 2020, pp. 185-204.
[http://dx.doi.org/10.1007/978-981-15-2361-8_8]
[3]
Patil, S.A.; Wang, J.; Li, X.S.; Chen, J.; Jones, T.S.; Hosni-Ahmed, A.; Patil, R.; Seibel, W.L.; Li, W.; Miller, D.D. New substituted 4H-chromenes as anticancer agents. Bioorg. Med. Chem. Lett., 2012, 22(13), 4458-4461.
[http://dx.doi.org/10.1016/j.bmcl.2012.04.074] [PMID: 22608389]
[4]
Conti, C.; Desideri, N. Synthesis and antirhinovirus activity of new 3-benzyl chromene and chroman derivatives. Bioorg. Med. Chem., 2009, 17(10), 3720-3727.
[http://dx.doi.org/10.1016/j.bmc.2009.03.051] [PMID: 19398344]
[5]
Kidwai, M.; Saxena, S.; Khan, M.K.; Thukral, S.S. Aqua mediated synthesis of substituted 2-amino-4H-chromenes and in vitro study as antibacterial agents. Bioorg. Med. Chem. Lett., 2005, 15(19), 4295-4298.
[http://dx.doi.org/10.1016/j.bmcl.2005.06.041] [PMID: 16040241]
[6]
Thomas, N.; Zachariah, S. Pharmacological activities of chromene derivatives: An overview. Asian J. Pharm. Clin. Res., 2013, 6, 11.
[7]
Thurston, D.E.; Bose, D.S.; Thompson, A.S.; Howard, P.W.; Leoni, A.; Croker, S.J.; Jenkins, T.C.; Neidle, S.; Hartley, J.A.; Hurley, L.H. Synthesis of sequence-selective C8-Linked Pyrrolo[2,1-c][1,4]benzodiazepine DNA interstrand cross-linking agents. J. Org. Chem., 1996, 61(23), 8141-8147.
[http://dx.doi.org/10.1021/jo951631s] [PMID: 11667802]
[8]
El Agrody, A.M.; Halawa, A.H.; Fouda, A.M.M.; Al-Dies, A.A. Anti-proliferative activity of novel 4H-benzo[h]chromenes, 7H-benzo[h]-chromeno[2,3-d]pyrimidines and the structure-activity relationships of the 2-, 3-positions and fused rings at the2, 3-positions. J. Saudi Chem. Soc., 2016, 21(1), 82-90.
[http://dx.doi.org/10.1016/j.jscs.2016.03.002]
[9]
Symeonidis, T.; Chamilos, M.; Hadjipavlou-Litina, D.J.; Kallitsakis, M.; Litinas, K.E. Synthesis of hydroxycoumarins and hydroxybenzo[f]- or [h]coumarins as lipid peroxidation inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(4), 1139-1142.
[http://dx.doi.org/10.1016/j.bmcl.2008.12.098] [PMID: 19150597]
[10]
Sruthi, V.; Sunitha, M.; Satheesh, A.; Ravi, K.M.; Mastan, R.K.; Chikurumilli, C.S.; Annapurna, N.; Paul Douglas, S. Catalyst free one-pot synthesis of chromenoquinolines and their antibacterial activity. Green and Sustain. Chem., 2017, 7(2), 141-151.
[http://dx.doi.org/10.4236/gsc.2017.72011]
[11]
Jain, P.R.; Patil, S.R.; Patil, A.A. A recent advances in the synthesis of chromenes and its Derivatives. World J. Pharm. Res., 2017, 6(13), 308-331.
[12]
Xu, Z.Q.; Pupek, K.; Suling, W.J.; Enache, L.; Flavin, M.T. Pyranocoumarin, a novel anti-TB pharmacophore: Synthesis and biological evaluation against Mycobacterium tuberculosis. Bioorg. Med. Chem., 2006, 14(13), 4610-4626.
[http://dx.doi.org/10.1016/j.bmc.2006.02.017] [PMID: 16513358]
[13]
Kamdar, N.R.; Haveliwala, D.D.; Mistry, P.T.; Patel, S.K. Synthesis and evaluation of in vitro antitubercular activity and antimicrobial activity of novel 4H-chromeno[2,3-d]pyrimidine via 2-amino-4-phenyl-4H-chromene-3-carbonitriles. Med. Chem. Res., 2010, 20(7), 854-864.
[http://dx.doi.org/10.1007/s00044-010-9399-x]
[14]
Patrusheva, O.S.; Zarubaev, V.V.; Shtro, A.A.; Orshanskaya, Y.R.; Boldyrev, S.A.; Ilyina, I.V.; Kurbakova, S.Yu.; Korchagina, D.V.; Volcho, K.P.; Salakhutdinov, N.F. Anti-influenza activity of monoterpene-derived substituted hexahydro-2H-chromenes. Bioorg. Med. Chem., 2016, 24(21), 5158-5161.
[http://dx.doi.org/10.1016/j.bmc.2016.08.037] [PMID: 27591012]
[15]
Abdelaziz, E.H.; Elnagdi, M.H.; Elagamey, A.A.; El-taweel, F.M. Nitriles in heterocyclic synthesis: Novel synthesis of benzo[c]coumarin and of benzo[c]pyrano[3,2-c]quinoline Derivatives. A. Heterocycles, 1987, 26(4), 903-907.
[http://dx.doi.org/10.3987/R-1987-04-0903]
[16]
Kumar, B.S.; Srinivasulu, N.; Udupi, R.H.; Rajitha, B.; Reddy, Y.T.; Reddy, P.N.; Kumar, P.S. Efficient synthesis of benzo[g]-and benzo[h]chromene derivatives by one-pot three-component condensation of aromatic aldehydes with active methylene compounds and naphthols. Russ. J. Org. Chem., 2006, 42(12), 1813-1815.
[http://dx.doi.org/10.1134/S1070428006120098]
[17]
Foye, W.O. Principi Di Chemico Farmaceutica; Piccin: Padova, Italy, 1991, p. 416.
[18]
Lazzeri Adreani, L.; Lapi, E. On some new esters of coumarin-3- carboxylic acid wit balsamic and bronchodilator action. Boll. Chim. Farm., 1960, 99, 583-586.
[PMID: 13759798]
[19]
Bonsignore, L.; Loy, G.; Secci, D.; Calignano, A. Synthesis and pharmacological activity of 2-oxo-(2H) 1-benzopyran-3-carboxamide derivatives. Eur. J. Med. Chem., 1993, 28(6), 517-520.
[http://dx.doi.org/10.1016/0223-5234(93)90020-F]
[20]
Hiramoto, K.; Nasuhara, A.; Michikoshi, K.; Kato, T.; Kikugawa, K. DNA strand-breaking activity and mutagenicity of 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP), a Maillard reaction product of glucose and glycine. Mutat. Res., 1997, 395(1), 47-56.
[http://dx.doi.org/10.1016/S1383-5718(97)00141-1] [PMID: 9465913]
[21]
Rathore, S.; Kumar, A.; Prakash, O. Vivekanand; Saxena, M.K.; Kasana, V.; Singh, S New insights into the promising antibacterial activity of thiophene or chromene moiety containing aryl sulfonamide. Res. Sq., 2021, 40, 1-21.
[22]
van Lingen, H.L.; Zhuang, W.; Hansen, T.; Rutjes, F.P.; Jørgensen, K.A. Formation of optically active chromanes by catalytic asymmetric tandem oxa-Michael addition-Friedel-Crafts alkylation reactions. Org. Biomol. Chem., 2003, 1(11), 1953-1958.
[http://dx.doi.org/10.1039/B303353H] [PMID: 12945779]
[23]
el-Gaby, M.S.; Zahran, M.A.; Ismail, M.M.; Ammar, Y.A. A novel synthesis of dibenzo[c,f]chromenes, dibenzo[c,h]chromenes and benzo[7,8]chromeno[3,4-f]isoindoles as antimicrobial agents. Farmaco, 2000, 55(3), 227-232.
[http://dx.doi.org/10.1016/S0014-827X(00)00008-2] [PMID: 10919087]
[24]
Yasunaga, T.; Kimura, T.; Naito, R.; Kontani, T.; Wanibuchi, F.; Yamashita, H.; Nomura, T.; Tsukamoto, S.; Yamaguchi, T.; Mase, T. Synthesis and pharmacological characterization of novel 6-fluorochroman derivatives as potential 5-HT1A receptor antagonists. J. Med. Chem., 1998, 41(15), 2765-2778.
[http://dx.doi.org/10.1021/jm9707840] [PMID: 9667967]
[25]
Ratnakar Reddy, K.; Sambasiva Rao, P.; Jitender Dev, G.; Poornachandra, Y.; Ganesh Kumar, C.; Shanthan Rao, P.; Narsaiah, B. Synthesis of novel 1,2,3-triazole/isoxazole functionalized 2H-chromene derivatives and their cytotoxic activity. Bioorg. Med. Chem. Lett., 2014, 24(7), 1661-1663.
[http://dx.doi.org/10.1016/j.bmcl.2014.02.069] [PMID: 24641975]
[26]
Minho Choi, M.; Hwang, Y.S.; Kumar, A.S.; Jo, H.; Jeong, Y.; Oh, Y.; Lee, J.; Yunb, J.; Kim, Y.; Han, S.B.; Jung, J.K.; Cho, J.; Lee, H. Design and synthesis of 3,4-dihydro-2h-benzo[h]chromene derivatives as potential NF-ĸB inhibitors. Bioorg. Med. Chem. Lett., 2014, 24(11), 2404-2407.
[http://dx.doi.org/10.1016/j.bmcl.2014.04.053]
[27]
Lima, C.F.; Costa, M.; Proença, M.F.; Pereira-Wilson, C. Novel structurally similar chromene derivatives with opposing effects on p53 and apoptosis mechanisms in colorectal HCT116 cancer cells. Eur. J. Pharm. Sci., 2015, 72, 34-45.
[http://dx.doi.org/10.1016/j.ejps.2015.02.019] [PMID: 25746954]
[28]
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]
[29]
Gopinath, G.; Sankeshi, V.; Perugu, S.; Alaparthi, M.D.; Bandaru, S.; Pasala, V.K.; Chittineni, P.R.; Krupadanam, G.L.D.; Sagurthi, S.R. Design and synthesis of chiral 2H-chromene-N-imidazolo-amino acid conjugates as aldose reductase inhibitors. Eur. J. Med. Chem., 2016, 124, 750-762.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.070] [PMID: 27639366]
[30]
Thanh, N.D.; Hai, D.S.; Ngoc Bich, V.T.; Thu Hien, P.T.; Ky Duyen, N.T.; Mai, N.T.; Dung, T.T.; Toan, V.N.; Kim Van, H.T.; Dang, L.H.; Toan, D.N.; Thanh Van, T.T. Efficient click chemistry towards novel 1H-1,2,3-triazole-tethered 4H-chromene-d-glucose conjugates: Design, synthesis and evaluation of in vitro antibacterial, MRSA and antifungal activities. Eur. J. Med. Chem., 2019, 167, 454-471.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.060] [PMID: 30784879]
[31]
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]
[32]
Schepetkin, I.A.; Kirpotina, L.N.; Khlebnikov, A.I.; Cheng, N.; Ye, R.D.; Quinn, M.T. Antagonism of human Formyl Peptide Receptor 1 (FPR1) by chromones and related isoflavones. Biochem. Pharmacol., 2014, 92(4), 627-641.
[http://dx.doi.org/10.1016/j.bcp.2014.09.027] [PMID: 25450672]
[33]
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]
[34]
Abdolmohammadi, S.H.; Balalaie, S. Novel and efficient catalysts for the one-pot synthesis of 3, 4-dihydropyrano [c] chromene derivatives in aqueous media. Tetrahedron Lett., 2007, 48(18), 3299-3303.
[http://dx.doi.org/10.1016/j.tetlet.2007.02.135]
[35]
Abd-El-Aziz, A.; El-Ghezlani, E.; Elaasser, M.; Afifi, T.; Okasha, R. 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]
[36]
Raj, V.; Lee, J. 2H/4H-chromenes-a versatile biologically attractive scaffold. Front Chem., 2020, 8, 623-645.
[http://dx.doi.org/10.3389/fchem.2020.00623] [PMID: 32850645]
[37]
Juliana, P.M.G.; Cássia, R.P.C.; Eliana, A.V.; José-Manuel, M.; Mariana, F.F.; Olea, N.; Carlos, I.Z.; Vilegas, W. Antitumoral, mutagenic and (anti)estrogenic activities of tingenone and pristimerin. Rev. Bras. Farmacogn., 2011, 21(6), 963-971.
[http://dx.doi.org/10.1590/S0102-695X2011005000153]
[38]
Kasibhatla, S.; Gourdeau, H.; Meerovitch, K.; Drewe, J.; Reddy, S.; Qiu, L.; Zhang, H.; Bergeron, F.; Bouffard, D.; Yang, Q.; Herich, J.; Lamothe, S.; Cai, S.X.; Tseng, B. Discovery and mechanism of action of a novel series of apoptosis inducers with potential vascular targeting activity. Mol. Cancer Ther., 2004, 3(11), 1365-1374.
[PMID: 15542775]
[39]
Luque-Agudo, V.; Albarrán-Velo, J.; Light, M.E.; Padrón, J.M.; Román, E.; Serrano, J.A.; Gil, M.V. Synthesis and antiproliferative activity of new 2-glyco-3-nitro-2H-chromenes. Bioorg. Chem., 2019, 87, 112-116.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.016] [PMID: 30878810]
[40]
Indulatha, V.N.; Gopal, N.; Jayakar, B. Anti-inflammatory activity of newly synthesised N-[4′-Oxo-2′-(substituted aryl/heteryl)- thiazolidin-3′-yl]-3-carboxamido-2H-chromen-2-one derivatives. Int. J. Chemtech Res., 2011, 3(4), 1930-1937.
[41]
Zarghi, A.; Arfaei, S. Selective COX-2 inhibitors: A review of their structure-activity relationships. Iran. J. Pharm. Res., 2011, 10(4), 655-683.
[PMID: 24250402]
[42]
Naseer, M.; Husain, A. Studies on chromene based 2, 6- disubstituted-thiazolo [3,2-B] [1,2,4] triazole derivatives: Synthesis and biological evaluation. J. Drug Deliv. Ther., 2021, 9(3-s), 236-242.
[43]
Chun, K.; Park, S.K.; Kim, H.M.; Choi, Y.; Kim, M.H.; Park, C.H.; Joe, B.Y.; Chun, T.G.; Choi, H.M.; Lee, H.Y.; Hong, S.H.; Kim, M.S.; Nam, K.Y.; Han, G. Chromen-based TNF-Alpha Converting Enzyme (TACE) inhibitors: Design, synthesis, and biological evaluation. Bioorg. Med. Chem., 2008, 16(1), 530-535.
[http://dx.doi.org/10.1016/j.bmc.2007.09.014] [PMID: 17936631]
[44]
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]
[45]
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]
[46]
Hosseini Ghazvini, S.M.B.; Safari, P.; Mobinikhaledi, A.; Moghanian, H.; Rasouli, H. Synthesis, characterization, anti-diabetic potential and DFT studies of 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde oxime. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2018, 205, 111-131.
[http://dx.doi.org/10.1016/j.saa.2018.07.009] [PMID: 30015017]
[47]
Takao, K.; Yahagi, H.; Uesawa, Y.; Sugita, Y. 3-(E)-Styryl-2H-chromene derivatives as potent and selective monoamine oxidase B inhibitors. Bioorg. Chem., 2018, 77, 436-442.
[http://dx.doi.org/10.1016/j.bioorg.2018.01.036] [PMID: 29448189]
[48]
Sudha, B.N.; Sastry, V.G.; Harika, M.S.; Yellasubbaiah, N. Synthesisof 3-(5-phenyl-1, 3, 4-oxadiazol-2-yl)-2H-chromen-2-ones as anticonvulsantagents. Indian J. Chem. Sect. B, 2018, 57, 737-745.
[49]
Chauhan, D.; Hashim, S.R.; Rani, P.; Kumar, S.; Shrimal, N.; Shastri, D.; Raj, V. Discovery of Substituted N-(6-Chloro-3-cyano-4-phenyl-4H-chromen-2-yl)- 2-(4-chloro-phenoxy)-acetamide for biphasic anticancer and anticonvulsant activities. Med. Chem., 2021, 17(3), 203-215.
[http://dx.doi.org/10.2174/1573406415666191206101617] [PMID: 31808391]
[50]
Minaev, B.F.; Valiev, R.R.; Nikonova, E.N.; Gadirov, R.M.; Solodova, T.A.; Kopylova, T.N.; Tel’minov, E.N. Computational and experimental investigation of the optical properties of the chromene dyes. J. Phys. Chem. A, 2015, 119(10), 1948-1956.
[http://dx.doi.org/10.1021/acs.jpca.5b00394] [PMID: 25710251]

Rights & Permissions Print Cite
Article Metrics
9
© 2024 Bentham Science Publishers | Privacy Policy