Generic placeholder image

Current Organic Chemistry

Editor-in-Chief

ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Review Article

Nitrogen-containing Fused Heterocycles: Organic Synthesis and Applications as Potential Anticancer Agents

Author(s): Pankaj V. Ledade, Trimurti L. Lambat*, Jitendra K. Gunjate, Paavan K.P.G. Chopra, Amitkumar V. Bhute, Mamata R. Lanjewar, Pooja M. Kadu, Utpal J. Dongre and Sami H. Mahmood

Volume 27, Issue 3, 2023

Published on: 08 February, 2023

Page: [206 - 222] Pages: 17

DOI: 10.2174/1385272827666221227120648

Price: $65

Abstract

The fused Nitrogen heterocyclic compounds and their derivatives have grown in prominence over the past several decades as a result of their significant medical value. The adaptable and easily synthesized N-Heterocyclic scaffolds are particularly exciting in both synthetic organic chemistry and the biological sector due to their powerful pharmacological properties, which are taken into consideration while considering their numerous uses. For the synthesis of N-heterocycles and their derivatives, several attempts were undertaken to create a variety of synthetic protocols. The N-Heterocyclic compounds provide a variety of adaptable structures for specific biological applications and represent novel, broad-spectrum antibacterial and anticancer agents. They typically have minimal toxicity profiles. The majority of these N-Heterocycles have demonstrated more cytotoxicity than the effective anticancer medication cisplatin. The design, synthesis, structural characterisation, and biological uses of N-Heterocycles are reviewed in this work. In this article, the developments made in this specific field are comprehensively examined.

Keywords: Organic synthesis, N-heterocycles, anti-cancer agents, novel synthetic protocols, fused N-heterocycles, biological activities.

Graphical Abstract
[1]
Rostamnia, S. In situ generation and protonation of the isocyanide/acetylene adduct: a powerful catalyst-free strategy for multicomponent synthesis of ketenimines, aza-dienes, and heterocycles. RSC Advances, 2015, 5(117), 97044-97065.
[http://dx.doi.org/10.1039/C5RA20455K]
[2]
Rostamnia, S.; Xin, H. Basic isoreticular metal-organic framework (IRMOF-3) porous nanomaterial as a suitable and green catalyst for selective unsymmetrical Hantzsch coupling reaction. Appl. Organomet. Chem., 2014, 28(5), 359-363.
[http://dx.doi.org/10.1002/aoc.3136]
[3]
Jalili, F.; Zarei, M.; Zolfigol, M.A.; Rostamnia, S.; Moosavi-Zare, A.R. SBA-15/PrN(CH2PO3H2)2 as a novel and efficient mesoporous solid acid catalyst with phosphorous acid tags and its application on the synthesis of new pyrimido[4,5-b]quinolones and pyrido[2,3-d]pyrimidines via anomeric based oxidation. Microporous Mesoporous Mater., 2020, 294, 109865.
[http://dx.doi.org/10.1016/j.micromeso.2019.109865]
[4]
Rostamnia, S.; Doustkhah, E. Synthesis of water-dispersed magnetic nanoparticles (H2O-DMNPs) of β-cyclodextrin modified Fe3O4 and its catalytic application in Kabachnik–Fields multicomponent reaction. J. Magn. Magn. Mater., 2015, 386, 111-116.
[http://dx.doi.org/10.1016/j.jmmm.2015.03.064]
[5]
Rostamnia, S.; Pourhassan, F. The SBA-15/SO3H nanoreactor as a highly efficient and reusable catalyst for diketene-based, four-component synthesis of polyhydroquinolines and dihydropyridines under neat conditions. Chin. Chem. Lett., 2013, 24(5), 401-403.
[http://dx.doi.org/10.1016/j.cclet.2013.03.020]
[6]
Rostamnia, S.; Doustkhah, E. A mesoporous silica/fluorinated alcohol adduct: an efficient metal-free, three-component synthesis of indazolophthalazinetrione heterocycles using a reusable nanoporous/trifluoroethanol adduct (SBA-15/TFE). Tetrahedron Lett., 2014, 55(15), 2508-2512.
[http://dx.doi.org/10.1016/j.tetlet.2014.03.019]
[7]
Alizadeh, A.; Zohreh, N.; Rostamnia, S. One-pot synthesis of functionalized furamide derivatives via a three-component reaction between an amine, diketene and dibenzoylacetylene in the presence of triphenylphosphine. Tetrahedron, 2007, 63(34), 8083-8087.
[http://dx.doi.org/10.1016/j.tet.2007.06.021]
[8]
Alizadeh, A.; Rostamnia, S.; Zhu, L.G. A novel pseudo-seven-component diastereoselective synthesis of λ5-phosphanylidene bis(2,5-dioxotetrahydro-1H-pyrrole-3-carboxylates) via binucleophilic systems. Tetrahedron Lett., 2010, 51(36), 4750-4754.
[http://dx.doi.org/10.1016/j.tetlet.2010.07.027]
[9]
Lambat, T.L.; Abdala, A.A.; Mahmood, S.; Ledade, P.V.; Chaudhary, R.G.; Banerjee, S. Sulfamic acid promoted one-pot multicomponent reaction: a facile synthesis of 4-oxo-tetrahydroindoles under ball milling conditions. RSC Advances, 2019, 9(68), 39735-39742.
[http://dx.doi.org/10.1039/C9RA08478A] [PMID: 35541403]
[10]
Patel, G.; Dewangan, D.K.; Bhakat, N.; Banerjee, S. Green approaches for the synthesis of poly-functionalized imidazole derivatives: A comprehensive review. Curr. Opin. Green Sustain. Chem., 2021, 4, 100175.
[http://dx.doi.org/10.1016/j.crgsc.2021.100175]
[11]
Il’in, M.V.; Sysoeva, A.A.; Novikov, A.S.; Bolotin, D.S. Diaryliodoniums as Hybrid Hydrogen- and Halogen-Bond-Donating Organocatalysts for the Groebke–Blackburn–Bienaymé Reaction. J. Org. Chem., 2022, 87(7), 4569-4579.
[http://dx.doi.org/10.1021/acs.joc.1c02885] [PMID: 35176856]
[12]
Dadiboyena, S.; Nefzi, A. Synthesis of functionalized tetrasubstituted pyrazolyl heterocycles – A review. Eur. J. Med. Chem., 2011, 46(11), 5258-5275.
[http://dx.doi.org/10.1016/j.ejmech.2011.09.016] [PMID: 21978837]
[13]
Omar, A. Review article; anticancer activities of some fused heterocyclic moieties containing nitrogen and/or sulfur heteroatoms. Al-Azhar. J. Pharm. Sci., 2020, 62(2), 39-54.
[http://dx.doi.org/10.21608/ajps.2020.118375]
[14]
Bioactive heterocyclic compound classes: pharmaceuticals; Lamberth, C.; Dinges, J., Eds.; John Wiley & Sons, 2012.
[http://dx.doi.org/10.1002/9783527664412]
[15]
Al-Jumaili, M.H.; Hamad, A.A.; Hashem, H.E.; Hussein, A.D.; Muhaidi, M.J.; Ahmed, M.A.; Albanaa, A.H.A.; Siddiqui, F.; Bakr, E.A. Comprehensive review on the Bis–heterocyclic compounds and their anticancer efficacy. J. Mol. Struct., 2022, 1271, 133970.
[http://dx.doi.org/10.1016/j.molstruc.2022.133970]
[16]
Liu, J.; Xiao, X.; Lai, Y.; Zhang, Z. Recent advances in transition metal-catalyzed heteroannulative difunctionalization of alkenes via C–H activation for the synthesis of heterocycles. Org. Chem. Front., 2022, 9(8), 2256-2279.
[http://dx.doi.org/10.1039/D2QO00081D]
[17]
Boas, U.; Heegaard, P.M.H. Dendrimers in drug research. Chem. Soc. Rev., 2004, 33(1), 43-63.
[http://dx.doi.org/10.1039/b309043b] [PMID: 14737508]
[18]
Aldeghi, M.; Malhotra, S.; Selwood, D.L.; Chan, A.W.E. Two- and three-dimensional rings in drugs. Chem. Biol. Drug Des., 2014, 83(4), 450-461.
[http://dx.doi.org/10.1111/cbdd.12260] [PMID: 24472495]
[19]
Hiesinger, K.; Dar’in, D.; Proschak, E.; Krasavin, M. Spirocyclic scaffolds in medicinal chemistry. J. Med. Chem., 2021, 64(1), 150-183.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01473] [PMID: 33381970]
[20]
Shelat, A.A.; Guy, R.K. Scaffold composition and biological relevance of screening libraries. Nat. Chem. Biol., 2007, 3(8), 442-446.
[http://dx.doi.org/10.1038/nchembio0807-442] [PMID: 17637770]
[21]
Craik, D.J.; Fairlie, D.P.; Liras, S.; Price, D. The future of peptide-based drugs. Chem. Biol. Drug Des., 2013, 81(1), 136-147.
[http://dx.doi.org/10.1111/cbdd.12055] [PMID: 23253135]
[22]
Macielag, M.J. Chemical properties of antimicrobials and their uniqueness.Antibiotic discovery and development; Springer: Boston, MA, 2012, pp. 793-820.
[http://dx.doi.org/10.1007/978-1-4614-1400-1_24]
[23]
Cheng, W.; Zeng, X.; Chen, H.; Li, Z.; Zeng, W.; Mei, L.; Zhao, Y. Versatile polydopamine platforms: synthesis and promising applications for surface modification and advanced nanomedicine. ACS Nano, 2019, 13(8), 8537-8565.
[http://dx.doi.org/10.1021/acsnano.9b04436] [PMID: 31369230]
[24]
Lambat, T.L.; Mahmood, S.H.; Ledade, P.V.; Banerjee, S. Microwave Assisted One‐Pot Multicomponent Synthesis Using ZnO‐β Zeolite Nanoparticle: An Easy Access to 7‐Benzodioxolo[4,5‐b]xanthene‐dione and 4‐Oxo‐tetrahydroindole Scaffolds. ChemistrySelect, 2020, 5(28), 8864-8874.
[http://dx.doi.org/10.1002/slct.202002160]
[25]
Lambat, T.L. Scolecite as novel heterogeneous catalyst for an efficient microwave assisted synthesis of 7-aryl-6H-benzo [H][1, 3] dioxolo [4, 5-b] xanthene-5, 6 (7H)-dione analogues via multi-component reaction. Int. J. Appl. Biol. Pharm. Technol., 2017, 8, 11-18.
[http://dx.doi.org/10.21276/ijabpt]
[26]
Keri, R.S.; Patil, M.R.; Patil, S.A.; Budagumpi, S. A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry. Eur. J. Med. Chem., 2015, 89, 207-251.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.059] [PMID: 25462241]
[27]
Kaur, R.; Kumar, K. Synthetic and medicinal perspective of quinolines as antiviral agents. Eur. J. Med. Chem., 2021, 215, 113220.
[http://dx.doi.org/10.1016/j.ejmech.2021.113220] [PMID: 33609889]
[28]
Gong, H.H.; Addla, D.; Lv, J.S.; Zhou, C.H. Heterocyclic naphthalimides as new skeleton structure of compounds with increasingly expanding relational medicinal applications. Curr. Top. Med. Chem., 2016, 16(28), 3303-3364.
[http://dx.doi.org/10.2174/1568026616666160506145943] [PMID: 27150364]
[29]
Hossain, M.; Nanda, A.K. A review on heterocyclic: synthesis and their application in medicinal chemistry of imidazole moiety. Science, 2018, 6(5), 83-94.
[http://dx.doi.org/10.11648/j.sjc.20180605.12]
[30]
Liang, X.; Wu, Q.; Luan, S.; Yin, Z.; He, C.; Yin, L.; Zou, Y.; Yuan, Z.; Li, L.; Song, X.; He, M.; Lv, C.; Zhang, W. A comprehensive review of topoisomerase inhibitors as anticancer agents in the past decade. Eur. J. Med. Chem., 2019, 171, 129-168.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.034] [PMID: 30917303]
[31]
Altaf, A.A.; Shahzad, A.; Gul, Z.; Rasool, N.; Badshah, A.; Lal, B.; Khan, E. A review on the medicinal importance of pyridine derivatives. J. Drug Des. Med. Chem, 2015, 1(1), 1-11.
[http://dx.doi.org/10.11648/j.jddmc.20150101.11]
[32]
Singh, M.; Singh, S.K. Benzothiazoles: how relevant in cancer drug design strategy? Anti-Cancer Agents in Medicinal Chemistry, 2014, 14(1), 127-146.
[33]
Hosseinzadeh, Z.; Ramazani, A.; Razzaghi-Asl, N. Anti-cancer nitrogen-containing heterocyclic compounds. Curr. Org. Chem., 2018, 22(23), 2256-2279.
[http://dx.doi.org/10.2174/1385272822666181008142138]
[34]
Galloway, W.R.J.D.; Isidro-Llobet, A.; Spring, D.R. Diversity-oriented synthesis as a tool for the discovery of novel biologically active small molecules. Nat. Commun., 2010, 1(1), 80.
[http://dx.doi.org/10.1038/ncomms1081] [PMID: 20865796]
[35]
Schenone, S.; Radi, M.; Musumeci, F.; Brullo, C.; Botta, M. Biologically driven synthesis of pyrazolo[3,4-d]pyrimidines as protein kinase inhibitors: an old scaffold as a new tool for medicinal chemistry and chemical biology studies. Chem. Rev., 2014, 114(14), 7189-7238.
[http://dx.doi.org/10.1021/cr400270z] [PMID: 24873489]
[36]
Carreira, E.M.; Fessard, T.C. Four-membered ring-containing spirocycles: synthetic strategies and opportunities. Chem. Rev., 2014, 114(16), 8257-8322.
[http://dx.doi.org/10.1021/cr500127b] [PMID: 25003801]
[37]
Norwood, V.M., IV; Huigens, R.W., III Harnessing the chemistry of the indole heterocycle to drive discoveries in biology and medicine. ChemBioChem, 2019, 20(18), 2273-2297.
[http://dx.doi.org/10.1002/cbic.201800768] [PMID: 30609199]
[38]
Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M. Novel thiazole derivatives: a patent review (2008 – 2012. Part 2). Expert Opin. Ther. Pat., 2014, 24(7), 759-777.
[http://dx.doi.org/10.1517/13543776.2014.910196] [PMID: 24745553]
[39]
Toscano, M.D.; Woycechowsky, K.J.; Hilvert, D. Minimalist active-site redesign: teaching old enzymes new tricks. Angew. Chem. Int. Ed., 2007, 46(18), 3212-3236.
[http://dx.doi.org/10.1002/anie.200604205] [PMID: 17450624]
[40]
Langeberg, L.K.; Scott, J.D. Signalling scaffolds and local organization of cellular behaviour. Nat. Rev. Mol. Cell Biol., 2015, 16(4), 232-244.
[http://dx.doi.org/10.1038/nrm3966] [PMID: 25785716]
[41]
Murray, J.K.; Gellman, S.H. Targeting protein–protein interactions: Lessons from p53/MDM2. Biopolymers, 2007, 88(5), 657-686.
[http://dx.doi.org/10.1002/bip.20741] [PMID: 17427181]
[42]
Hunter, J.C.; Gurbani, D.; Ficarro, S.B.; Carrasco, M.A.; Lim, S.M.; Choi, H.G.; Xie, T.; Marto, J.A.; Chen, Z.; Gray, N.S.; Westover, K.D. in situ selectivity profiling and crystal structure of SML-8-73-1, an active site inhibitor of oncogenic K-Ras G12C. Proc. Natl. Acad. Sci. USA, 2014, 111(24), 8895-8900.
[http://dx.doi.org/10.1073/pnas.1404639111] [PMID: 24889603]
[43]
Kaur, M.; Singh, M.; Chadha, N.; Silakari, O. Oxindole: A chemical prism carrying plethora of therapeutic benefits. Eur. J. Med. Chem., 2016, 123, 858-894.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.011] [PMID: 27543880]
[44]
Lambat, T.; Deo, S.; Deshmukh, T. Sulphamic acid assisted synthesis of polyhydroquinolines via Hantzsch multicomponent reaction: a green approach. J. Chem. Pharm. Res., 2014, 6(4), 888-892.
[45]
Asatkar, A.; Lambat, T.L.; Mahmood, S.; Mondal, A.; Singh, M.; Banerjee, S. Facile protocol for the synthesis of benzothiazole, benzoxazole and N-benzimidazole derivatives using rice husk derived chemically activated carbon. Mater. Today Proc., 2020, 29, 738-742.
[http://dx.doi.org/10.1016/j.matpr.2020.04.510]
[46]
He, Y.; Li, W.; Zhou, H.; Zeng, G.; Chen, Z.; Ge, J-Y.; Lv, N.; Chen, J. Redox‐neutral synthesis of polycyclic azaheterocycles via cobalt‐catalyzed hydroarylation/annulation of maleimides. Adv. Synth. Catal., 2022, 364(21), 3730-3735.
[http://dx.doi.org/10.1002/adsc.202200809]
[47]
Reutskaya, E.; Sapegin, A.; Peintner, S.; Erdélyi, M.; Krasavin, M. Sulfur Oxidation Increases the Rate of HIRE-Type [1.4]Thiazepinone Ring Expansion and Influences the Conformation of a Medium-Sized Heterocyclic Scaffold. J. Org. Chem., 2021, 86(8), 5778-5791.
[http://dx.doi.org/10.1021/acs.joc.1c00236] [PMID: 33826339]
[48]
Wu, J.; Liu, Y.; Qian, B.; Yang, H.; Lu, L.; Zhang, J.; Shang, Y. Catalytic ring expansion of indole toward dibenzoazepine analogues enabled by cationic palladium(ii) complexes. ACS Catal., 2022, 12, 6216-6226.
[http://dx.doi.org/10.1021/acscatal.1c06021]
[49]
Il’in, M.V.; Novikov, A.S.; Bolotin, D.S. Sulfonium and selenonium salts as noncovalent organocatalysts for the multicomponent groebke–blackburn–bienaymé reaction. J. Org. Chem., 2022, 87(15), 10199-10207.
[http://dx.doi.org/10.1021/acs.joc.2c01141] [PMID: 35858372]
[50]
Lambat, T.L.; Chopra, P.K.P.G.; Mahmood, S.H. Microwave: a green contrivance for the synthesis of N-heterocyclic compounds. Curr. Org. Chem., 2020, 24(22), 2527-2554.
[http://dx.doi.org/10.2174/1385272824999200622114919]
[51]
Chen, J.R.; Hu, X.Q.; Lu, L.Q.; Xiao, W.J. Formal [4+1] annulation reactions in the synthesis of carbocyclic and heterocyclic systems. Chem. Rev., 2015, 115(11), 5301-5365.
[http://dx.doi.org/10.1021/cr5006974] [PMID: 25992465]
[52]
Dadmal, T.L.; Appalanaidu, K.; Kumbhare, R.M.; Mondal, T.; Ramaiah, M.J.; Bhadra, M.P. Synthesis and biological evaluation of triazole and isoxazole-tagged benzothiazole/benzoxazole derivatives as potent cytotoxic agents. New J. Chem., 2018, 42(19), 15546-15551.
[http://dx.doi.org/10.1039/C8NJ01249K]
[53]
Chattopadhyay, S.K.; Karmakar, S.; Biswas, T.; Majumdar, K.C.; Rahaman, H.; Roy, B. Formation of medium-ring heterocycles by diene and enyne metathesis. Tetrahedron, 2007, 63(19), 3919-3952.
[http://dx.doi.org/10.1016/j.tet.2007.01.063]
[54]
Reddy, M.S.; Thirukovela, N.S.; Narsimha, S.; Ravinder, M.; Nukala, S.K. Synthesis of fused 1, 2, 3-triazoles of Clioquinol via sequential CuAAC and CH arylation; in vitro anticancer activity, in silico DNA topoisomerase II inhibitory activity and ADMET. J. Mol. Struct., 2022, 1250, 131747.
[http://dx.doi.org/10.1016/j.molstruc.2021.131747]
[55]
Maleki, A.; Ghassemi, M.; Firouzi-Haji, R. Green multicomponent synthesis of four different classes of six-membered N -containing and O -containing heterocycles catalyzed by an efficient chitosan-based magnetic bionanocomposite. Pure Appl. Chem., 2018, 90(2), 387-394.
[http://dx.doi.org/10.1515/pac-2017-0702]
[56]
Jangir, N.; Bagaria, S.K.; Jangid, D.K. Nanocatalysts: applications for the synthesis of N-containing five-membered heterocycles. RSC Advances, 2022, 12(30), 19640-19666.
[http://dx.doi.org/10.1039/D2RA03122A] [PMID: 35865567]
[57]
Schumacher, C.; Molitor, C.; Smid, S.; Truong, K.N.; Rissanen, K.; Bolm, C. Mechanochemical syntheses of n -containing heterocycles with tosmic. J. Org. Chem., 2021, 86(20), 14213-14222.
[http://dx.doi.org/10.1021/acs.joc.1c01529] [PMID: 34405999]
[58]
Zeng, D.; Wang, M.W.; Xiang, M.; Liu, L.W.; Wang, P.Y.; Li, Z.; Yang, S. Design, synthesis, and antimicrobial behavior of novel oxadiazoles containing various N ‐containing heterocyclic pendants. Pest Manag. Sci., 2020, 76(8), 2681-2692.
[http://dx.doi.org/10.1002/ps.5814] [PMID: 32149457]
[59]
Snoussi, Y.; Besbes, N. Use of aluminosilicates such as acid-activated clays as solid catalysts for the reactivity of the various carbonyl compounds in heterocyclic synthesis. Moroccan J. Heterocycl. Chem., 2020, 19(3), 19-3.
[http://dx.doi.org/10.48369/IMIST.PRSM/jmch-v19i3.24243]
[60]
Philip, R.M.; Treesa, G.S.S.; Saranya, S.; Anilkumar, G. Applications of aryl-sulfinamides in the synthesis of N-heterocycles. RSC Advances, 2021, 11(33), 20591-20600.
[http://dx.doi.org/10.1039/D1RA04099E] [PMID: 35479913]
[61]
Alamgir, A.N.M. Phytoconstituents—active and inert constituents, metabolic pathways, chemistry and application of phytoconstituents, primary metabolic products, and bioactive compounds of primary metabolic origin.Therapeutic use of medicinal plants and their extracts; Springer: Cham, 2018, Vol. 2, pp. 25-164.
[http://dx.doi.org/10.1007/978-3-319-92387-1_2]
[62]
Majumder, A.; Gupta, R.; Jain, A. Microwave-assisted synthesis of nitrogen-containing heterocycles. Green Chem. Lett. Rev., 2013, 6(2), 151-182.
[http://dx.doi.org/10.1080/17518253.2012.733032]
[63]
Prandi, C.; Occhiato, E.G. From synthetic control to natural products: a focus on N -heterocycles. Pest Manag. Sci., 2019, 75(9), 2385-2402.
[http://dx.doi.org/10.1002/ps.5322] [PMID: 30624033]
[64]
Balci, M. Recent advances in the synthesis of fused heterocycles with new skeletons via alkyne cyclization. Tetrahedron Lett., 2020, 61(24), 151994.
[http://dx.doi.org/10.1016/j.tetlet.2020.151994]
[65]
Kasatkina, S.O.; Geyl, K.K.; Baykov, S.V.; Novikov, M.S.; Boyarskiy, V.P. “Urea to Urea” Approach: Access to Unsymmetrical Ureas Bearing Pyridyl Substituents. Adv. Synth. Catal., 2022, 364(7), 1295-1304.
[http://dx.doi.org/10.1002/adsc.202101490]
[66]
Kasatkina, S.O.; Geyl, K.K.; Baykov, S.V.; Boyarskaya, I.A.; Boyarskiy, V.P. Catalyst-free synthesis of substituted pyridin-2-yl, quinolin-2-yl, and isoquinolin-1-yl carbamates from the corresponding hetaryl ureas and alcohols. Org. Biomol. Chem., 2021, 19(27), 6059-6065.
[http://dx.doi.org/10.1039/D1OB00783A] [PMID: 34137410]
[67]
Grintsevich, S.; Sapegin, A.; Krasavin, M. Significant broadening of the substrate scope for the hydrated imidazoline ring expansion (hire) via the use of lithium hexamethyldisilazide. Synthesis, 2022, 54(10), 2494-2510.
[http://dx.doi.org/10.1055/s-0040-1719882]
[68]
Ye, D.; Lu, H.; He, Y.; Zheng, Z.; Wu, J.; Wei, H. Rapid syntheses of N-fused heterocycles via acyl-transfer in heteroaryl ketones. Nat. Commun., 2022, 13(1), 3337.
[http://dx.doi.org/10.1038/s41467-022-31063-3] [PMID: 35680930]
[69]
Li, Y.; Liu, G.F.; Tan, C.P.; Ji, L.N.; Mao, Z.W. Antitumor properties and mechanisms of mitochondria-targeted Ag( I ) and Au( I ) complexes containing N-heterocyclic carbenes derived from cyclophanes. Metallomics, 2014, 6(8), 1460-1468.
[http://dx.doi.org/10.1039/C4MT00046C] [PMID: 24788133]
[70]
Liu, W.; Gust, R. Update on metal N-heterocyclic carbene complexes as potential anti-tumor metallodrugs. Coord. Chem. Rev., 2016, 329, 191-213.
[http://dx.doi.org/10.1016/j.ccr.2016.09.004]
[71]
Akhtar, J.; Khan, A.A.; Ali, Z.; Haider, R.; Shahar Yar, M. Structure-activity relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities. Eur. J. Med. Chem., 2017, 125, 143-189.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.023] [PMID: 27662031]
[72]
Gou, Y. Wang, J.; Chen, S.; Zhang, Z.; Zhang, Y.; Zhang, W.; Yang, F. α−N−heterocyclic thiosemicarbazone Fe(III) complex: Characterization of its antitumor activity and identification of anticancer mechanism. Eur. J. Med. Chem., 2016, 123, 354-364.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.041] [PMID: 27487566]
[73]
Pennington, L.D.; Moustakas, D.T. The necessary nitrogen atom: a versatile high-impact design element for multiparameter optimization. J. Med. Chem., 2017, 60(9), 3552-3579.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01807] [PMID: 28177632]
[74]
Martins, P.; Jesus, J.; Santos, S.; Raposo, L.R.; Roma-Rodrigues, C.; Baptista, P.V.; Fernandes, A.R. Heterocyclic anticancer compounds: recent advances and the paradigm shift towards the use of nanomedicine’s tool box. Molecules, 2015, 20(9), 16852-16891.
[http://dx.doi.org/10.3390/molecules200916852]
[75]
Khan, I.; Ibrar, A.; Ahmed, W.; Saeed, A. Synthetic approaches, functionalization and therapeutic potential of quinazoline and quinazolinone skeletons: The advances continue. Eur. J. Med. Chem., 2015, 90, 124-169.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.084] [PMID: 25461317]
[76]
Wang, X.; Zhang, H.; Chen, X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resist., 2019, 2(2), 141-160.
[http://dx.doi.org/10.20517/cdr.2019.10] [PMID: 34322663]
[77]
Garrett, M.D.; Workman, P. Discovering novel chemotherapeutic drugs for the third millennium. Eur. J. Cancer, 1999, 35(14), 2010-2030.
[http://dx.doi.org/10.1016/S0959-8049(99)00280-4] [PMID: 10711243]
[78]
Yan, S.J.; Liu, Y.J.; Chen, Y.L.; Liu, L.; Lin, J. An efficient one-pot synthesis of heterocycle-fused 1,2,3-triazole derivatives as anti-cancer agents. Bioorg. Med. Chem. Lett., 2010, 20(17), 5225-5228.
[http://dx.doi.org/10.1016/j.bmcl.2010.06.141] [PMID: 20655212]
[79]
Fu, D.J.; Li, P.; Wu, B.W.; Cui, X.X.; Zhao, C.B.; Zhang, S.Y. Molecular diversity of trimethoxyphenyl-1,2,3-triazole hybrids as novel colchicine site tubulin polymerization inhibitors. Eur. J. Med. Chem., 2019, 165, 309-322.
[80]
Banerji, B.; Pramanik, S. K.; Sanphui, P.; Nikhar, S.; Biswas, S. C. Synthesis and cytotoxicity studies of novel triazolo‐benzoxazepine as new anticancer agents. Chem. Biol. Drug. Des., 2013, 82(4), 401-409.
[http://dx.doi.org/10.1111/cbdd.12164] [http://dx.doi.org/10.1016/j.ejmech.2019.01.033] [PMID: 30690300]
[81]
Kamel, M.M.; Megally Abdo, N.Y. Synthesis of novel 1,2,4-triazoles, triazolothiadiazines and triazolothiadiazoles as potential anticancer agents. Eur. J. Med. Chem., 2014, 86, 75-80.
[http://dx.doi.org/10.1016/j.ejmech.2014.08.047] [PMID: 25147148]
[82]
Ramaprasad, G.C.; Kalluraya, B.; Sunil Kumar, B. Microwave-assisted synthesis of triazolothiadiazole analogs as anticancer agents. Med. Chem. Res., 2014, 23(8), 3644-3651.
[http://dx.doi.org/10.1007/s00044-014-0944-x]
[83]
Baviskar, A.T.; Madaan, C.; Preet, R.; Mohapatra, P.; Jain, V.; Agarwal, A.; Guchhait, S.K.; Kundu, C.N.; Banerjee, U.C.; Bharatam, P.V. N-fused imidazoles as novel anticancer agents that inhibit catalytic activity of topoisomerase IIα and induce apoptosis in G1/S phase. J. Med. Chem., 2011, 54(14), 5013-5030.
[http://dx.doi.org/10.1021/jm200235u] [PMID: 21644529]
[84]
Rostamnia, S.; Hassankhani, A. RuCl3-catalyzed solvent-free Ugi-type Groebke–Blackburn synthesis of aminoimidazole heterocycles. RSC Advances, 2013, 3(40), 18626-18629.
[http://dx.doi.org/10.1039/c3ra42752h]
[85]
Rostamnia, S.; Xin, H.; Nouruzi, N. Metal–organic frameworks as a very suitable reaction inductor for selective solvent-free multicomponent reaction: IRMOF-3 as a heterogeneous nanocatalyst for Kabachnik–Fields three-component reaction. Microporous Mesoporous Mater., 2013, 179, 99-103.
[http://dx.doi.org/10.1016/j.micromeso.2013.05.009]
[86]
Husain, A.; Rashid, M.; Shaharyar, M.; Siddiqui, A.A.; Mishra, R. Benzimidazole clubbed with triazolo-thiadiazoles and triazolo-thiadiazines: New anticancer agents. Eur. J. Med. Chem., 2013, 62, 785-798.
[http://dx.doi.org/10.1016/j.ejmech.2012.07.011] [PMID: 23333063]
[87]
Husain, A.; Rashid, M.; Mishra, R.; Parveen, S.; Shin, D.S.; Kumar, D. Benzimidazole bearing oxadiazole and triazolo-thiadiazoles nucleus: Design and synthesis as anticancer agents. Bioorg. Med. Chem. Lett., 2012, 22(17), 5438-5444.
[http://dx.doi.org/10.1016/j.bmcl.2012.07.038] [PMID: 22840417]
[88]
Ding, H.W.; Yu, L.; Bai, M.; Qin, X.C.; Song, M.; Zhao, Q.C. Design, synthesis and evaluation of some 1,6-disubstituted-1H-benzo[d]imidazoles derivatives targeted PI3K as anticancer agents. Bioorg. Chem., 2019, 93, 103283.
[http://dx.doi.org/10.1016/j.bioorg.2019.103283] [PMID: 31585260]
[89]
Chitrakar, R.; Rawat, D.; Sistla, R.; Vadithe, L.N.; Subbarayappa, A. Design, synthesis and anticancer activity of sulfenylated imidazo-fused heterocycles. Bioorg. Med. Chem. Lett., 2021, 49, 128307.
[http://dx.doi.org/10.1016/j.bmcl.2021.128307] [PMID: 34363936]
[90]
Zhu, S.L.; Wu, Y.; Liu, C.J.; Wei, C.Y.; Tao, J.C.; Liu, H.M. Design and stereoselective synthesis of novel isosteviol-fused pyrazolines and pyrazoles as potential anticancer agents. Eur. J. Med. Chem., 2013, 65, 70-82.
[http://dx.doi.org/10.1016/j.ejmech.2013.04.044] [PMID: 23693151]
[91]
Abbas, E.M.H.; Dawood, D.H.; Farghaly, T.A.; El-hag, F.A.; Ali, M.M. Synthesis and structure–activity relationship study of novel pyrazolylthiazoles as potential anti‐breast cancer agents. J. Heterocycl. Chem., 2017, 54(3), 1974-1982.
[http://dx.doi.org/10.1002/jhet.2794]
[92]
Abdou, W.M.; Barghash, R.F.; Khidre, R.E. Antineoplastic activity of fused nitrogen-phosphorus heterocycles and derived phosphonates. Monatsh. Chem., 2013, 144(8), 1233-1242.
[http://dx.doi.org/10.1007/s00706-013-0950-6]
[93]
Sztanke, M.; Rzymowska, J.; Sztanke, K. Synthesis, structure elucidation and identification of antiproliferative activities of a novel class of thiophene bioisosteres bearing the privileged 7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-one scaffold. Bioorg. Med. Chem., 2015, 23(13), 3448-3456.
[http://dx.doi.org/10.1016/j.bmc.2015.04.037] [PMID: 25975637]
[94]
Doan, P.; Karjalainen, A.; Chandraseelan, J.G.; Sandberg, O.; Yli-Harja, O.; Rosholm, T.; Franzen, R.; Candeias, N.R.; Kandhavelu, M. Synthesis and biological screening for cytotoxic activity of N-substituted indolines and morpholines. Eur. J. Med. Chem., 2016, 120, 296-303.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.024] [PMID: 27214140]
[95]
Su, T.; Zhu, J.; Sun, R.; Zhang, H.; Huang, Q.; Zhang, X.; Du, R.; Qiu, L.; Cao, R. Design, synthesis and biological evaluation of new quinoline derivatives as potential antitumor agents. Eur. J. Med. Chem., 2019, 178, 154-167.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.088] [PMID: 31181480]
[96]
Jafari, F.; Baghayi, H.; Lavaee, P.; Hadizadeh, F.; Soltani, F.; Moallemzadeh, H.; Mirzaei, S.; Aboutorabzadeh, S.M.; Ghodsi, R. Design, synthesis and biological evaluation of novel benzo- and tetrahydrobenzo-[h]quinoline derivatives as potential DNA-intercalating antitumor agents. Eur. J. Med. Chem., 2019, 164, 292-303.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.060] [PMID: 30599418]
[97]
Upadhyay, K.D.; Dodia, N.M.; Khunt, R.C.; Chaniara, R.S.; Shah, A.K. Synthesis and biological screening of pyrano [3, 2-c] quinoline analogues as anti-inflammatory and anticancer agents. ACS Med. Chem. Lett., 2018, 9(3), 283-288.
[http://dx.doi.org/10.1021/acsmedchemlett.7b00545] [PMID: 29541375]
[98]
Othman, D.I.A.; Selim, K.B.; El-Sayed, M.A.A.; Tantawy, A.S.; Amen, Y.; Shimizu, K.; Okauchi, T.; Kitamura, M.; Kitamura, M. Design, synthesis and anticancer evaluation of new substituted thiophene-quinoline derivatives. Bioorg. Med. Chem., 2019, 27(19), 115026.
[http://dx.doi.org/10.1016/j.bmc.2019.07.042] [PMID: 31416740]
[99]
Lafayette, E.; Almeida, V.S.; da Rocha, P. M.; Carneiro B.E.; Gonçalves da S. T.; de Moura, O.R.; da Rocha P. I.; de Carvalho, L., Jr; do Carmo A.L.M. Synthesis, DNA binding and topoisomerase I inhibition activity of thiazacridine and imidazacridine derivatives. Molecules, 2013, 18(12), 15035-15050.
[http://dx.doi.org/10.3390/molecules181215035] [PMID: 24322489]
[100]
Nkosi, S.M.; Anand, K.; Anandakumar, S.; Singh, S.; Chuturgoon, A.A.; Gengan, R.M. Design, synthesis, anticancer, antimicrobial activities and molecular docking studies of novel quinoline bearing dihydropyridines. J. Photochem. Photobiol., 2016, 165, 266-276.
[http://dx.doi.org/10.1016/j.jphotobiol.2016.10.009]
[101]
Mirzaei, S.; Hadizadeh, F.; Eisvand, F.; Mosaffa, F.; Ghodsi, R. Synthesis, structure-activity relationship and molecular docking studies of novel quinoline-chalcone hybrids as potential anticancer agents and tubulin inhibitors. J. Mol. Struct., 2020, 1202, 127310.
[http://dx.doi.org/10.1016/j.molstruc.2019.127310]
[102]
Ge, C.; Chang, L.; Zhao, Y.; Chang, C.; Xu, X.; He, H.; Wang, Y.; Dai, F.; Xie, S.; Wang, C.; Wang, C. Design, synthesis and evaluation of naphthalimide derivatives as potential anticancer agents for hepatocellular carcinoma. Molecules, 2017, 22(2), 342.
[http://dx.doi.org/10.3390/molecules22020342] [PMID: 28241441]
[103]
Ammar, Y.A.Sh.; El-Sharief, A.M.; Belal, A.; Abbas, S.Y.; Mohamed, Y.A.; Mehany, A.B.M.; Ragab, A. Design, synthesis, antiproliferative activity, molecular docking and cell cycle analysis of some novel (morpholinosulfonyl) isatins with potential EGFR inhibitory activity. Eur. J. Med. Chem., 2018, 156, 918-932.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.061] [PMID: 30096580]
[104]
Chate, A.V.; Kamdi, S.P.; Bhagat, A.N.; Jadhav, C.K.; Nipte, A.; Sarkate, A.P.; Tiwari, S.V.; Gill, C.H. Design, synthesis and SAR study of novel spiro [pyrimido[5,4-b]quinoline-10,5′-pyrrolo[2,3-d]pyrimidine] derivatives as promising anticancer agents. J. Heterocycl. Chem., 2018, 55(10), 2297-2302.
[http://dx.doi.org/10.1002/jhet.3286]
[105]
Patravale, A.A.; Gore, A.H.; Kolekar, G.B.; Deshmukh, M.B.; Choudhari, P.B.; Bhatia, M.S.; Prabhu, S.; Jamdhade, M.D.; Patole, M.S.; Anbhule, P.V. Synthesis, biological evaluation and molecular docking studies of some novel indenospiro derivatives as anticancer agents. J. Taiwan Inst. Chem. Eng., 2016, 68, 105-118.
[http://dx.doi.org/10.1016/j.jtice.2016.09.034]
[106]
Li, E.; Lin, Q.; Meng, Y.; Zhang, L.; Song, P.; Li, N.; Xin, J.; Yang, P.; Bao, C.; Zhang, D.; Zhang, Y.; Wang, J.; Zhang, Q.; Liu, H. 2,4-Disubstituted quinazolines targeting breast cancer cells via EGFR-PI3K. Eur. J. Med. Chem., 2019, 172, 36-47.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.030] [PMID: 30939352]
[107]
Fan, C.; Zhong, T.; Yang, H.; Yang, Y.; Wang, D.; Yang, X.; Xu, Y.; Fan, Y. Design, synthesis, biological evaluation of 6-(2-amino-1H-benzo[d]imidazole-6-yl)quinazolin-4(3H)-one derivatives as novel anticancer agents with Aurora kinase inhibition. Eur. J. Med. Chem., 2020, 190, 112108.
[http://dx.doi.org/10.1016/j.ejmech.2020.112108] [PMID: 32058239]
[108]
Tantawy, E.S.; Amer, A.M.; Mohamed, E.K.; Abd Alla, M.M.; Nafie, M.S. Synthesis, characterization of some pyrazine derivatives as anti-cancer agents: in vitro and in silico approaches. J. Mol. Struct., 2020, 1210, 128013.
[http://dx.doi.org/10.1016/j.molstruc.2020.128013]
[109]
Veligeti, R.; Madhu, R.B.; Anireddy, J.; Pasupuleti, V.R.; Avula, V.K.R.; Ethiraj, K.S.; Uppalanchi, S.; Kasturi, S.; Perumal, Y.; Anantaraju, H.S.; Polkam, N.; Guda, M.R.; Vallela, S.; Zyryanov, G.V. Synthesis of novel cytotoxic tetracyclic acridone derivatives and study of their molecular docking, ADMET, QSAR, bioactivity and protein binding properties. Sci. Rep., 2020, 10(1), 20720.
[http://dx.doi.org/10.1038/s41598-020-77590-1] [PMID: 33244007]
[110]
Kumar, S.; Mehndiratta, S.; Nepali, K.; Gupta, M.K.; Koul, S.; Sharma, P.R.; Saxena, A.K.; Dhar, K.L. Novel indole-bearing combretastatin analogues as tubulin polymerization inhibitors. Org. Med. Chem. Lett., 2013, 3(1), 3.
[http://dx.doi.org/10.1186/2191-2858-3-3] [PMID: 23414667]
[111]
Shivarama, H. B.; Narayana Poojary, K.; Sooryanarayana Rao, B.; Shivananda, M.K. New bis-aminomercaptotriazoles and bis-triazolothiadiazoles as possible anticancer agents. Eur. J. Med. Chem., 2002, 37(6), 511-517.
[http://dx.doi.org/10.1016/S0223-5234(02)01358-2] [PMID: 12204477]

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