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Letters in Drug Design & Discovery

Author(s): Kereyagalahally H. Narasimhamurthy, Yarabahally R. Girish, Toreshettahally R. Swaroop* and Kanchugarakoppal S. Rangappa*

DOI: 10.2174/1570180820666230516111340

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Diversely Functionalized Pyridine Ring-fused Heterocycles and their Anticancer Properties

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Abstract

Among N-containing heterocycles, pyridine occupies a prominent position due to its presence in nature. Many enzymes in living systems, which are involved in redox reactions, contain pyridine moiety. In addition, its importance in medicinal chemistry and its presence in drugs are well documented. Several pyridine containing compounds are well-known as tubulin polymerization inhibitors and are found to bind with androgen receptors, kinases, carbonic anhydrase and topoisomerase. In recent years, researching have been modifying pyridine containing entities to treat cancer. This review sheds light on recent developments in anticancer studies of pyridine ring-fused heterocyclic compounds.

Keywords: Leukemia, anticancer, pyridine, pyridine conjugated, heterocycles, nitrogen containing heterocycles.

Graphical Abstract

[1]
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.
[2]
World Health Organization Global health estimates 2015: Deaths by cause, age, sex, by country and by region, 2000–2015; WHO: Geneva, 2016.
[3]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[4]
Schmidt, E.V.; Chisamore, M.J.; Chaney, M.F.; Maradeo, M.E.; Anderson, J.; Baltus, G.A.; Pinheiro, E.M.; Uebele, V.N. Assessment of clinical activity of PD-1 checkpoint inhibitor combination therapies reported in clinical trials. JAMA Netw. Open, 2020, 3(2), e1920833.
[http://dx.doi.org/10.1001/jamanetworkopen.2019.20833] [PMID: 32049290]
[5]
Alaa, M.; Muataz, A.; Wedad, A.; Israa, S.; Muna, B.; Dheaa, Z.; Emad, Y. Cytotoxic activity against human lung cancer cell line (A549) of dimethyl-tin(IV)valsartan complex. Int. J. Med. Toxicol. Leg. Med., 2022, 25(3 and 4), 102-106.
[6]
Mohammed, A.; Makia, R.; Al-Agele, M.; Raheem, R.; Yousif, E. Cytotoxic effects of valsartan organotin(IV) complexes on human lung cancer cells. Biointerface Res. Appl. Chem., 2020, 11(1), 8156-8164.
[http://dx.doi.org/10.33263/BRIAC111.81568164]
[7]
Vitaku, E.; Smith, D.T.; Njardarson, J.T. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals. J. Med. Chem., 2014, 57(24), 10257-10274.
[http://dx.doi.org/10.1021/jm501100b] [PMID: 25255204]
[8]
Dua, R.; Shrivastava, S.; Sonwane, S.K.; Srivastava, S.K. Pharmacological significance of synthetic heterocycles scaffold: A review. Adv. Biol. Res., 2011, 5(3), 120-144.
[9]
Shivaprasad, C.M.; Jagadish, S.; Swaroop, T.R.; Mohan, C.D.; Roopashree, R.; Kumar, K.S.S.; Rangappa, K.S. New synthetic benzisoxazole derivatives as antimicrobial, antioxidant and anti-inflammatory agents. Eur. J. Chem., 2013, 4(4), 402-407.
[http://dx.doi.org/10.5155/eurjchem.4.4.402-407.864]
[10]
Shivaprasad, C.M.; Jagadish, S.; Swaroop, T.R.; Mohan, C.D.; Roopashree, R.; Kumar, K.S.S.; Rangappa, K.S. Synthesis of new benzisoxazole derivatives and their antimicrobial, antioxidant and anti-inflammatory activities. Eur. J. Chem., 2014, 5(1), 91-95.
[http://dx.doi.org/10.5155/eurjchem.5.1.91-95.866]
[11]
Roopashree, R.; Ramesh Swaroop, T.; Jagadish, S.; Dhananjaya, M.C.; Subbegowda, R.K. Synthesis and cholinesterase inhibition activity of new pyrrolopyrimidine derivatives. Lett. Drug Des. Discov., 2014, 11(10), 1143-1148.
[http://dx.doi.org/10.2174/1570180811666140704171902]
[12]
Rakesh, K.S.; Jagadish, S.; Swaroop, T.R.; Ashwini, N.; Harsha, K.B.; Rangappa, K.S. Antioxidant and anti-inflammatory activities of synthetic 2,4-bis(aryl/heteroaryl)-5-acylthiazole derivatives. Asian J. Biochem. Pharm. Res., 2014, 4(3), 316-327.
[13]
Rakesh, K.S.; Jagadish, S.; Swaroop, T.R.; Mohan, C.D.; Ashwini, N.; Harsha, K.B.; Farhan, Z.; Girish, K.S.; Rangappa, K.S. Anticancer activity of 2,4-disubstituted thiophene derivatives: Dual inhibitors of Lipoxygenase and Cyclooxygenase. Med. Chem., 2015, 11(5), 462-472.
[http://dx.doi.org/10.2174/1573406411666141210141918] [PMID: 25494807]
[14]
Rakesh, K.S.; Jagadish, S.; Balaji, K.S.; Zameer, F.; Swaroop, T.R.; Mohan, C.D.; Jayarama, S.; Rangappa, K.S. 3,5-Disubstituted isoxazole derivatives: Potential inhibitors of inflammation and cancer. Inflammation, 2016, 39(1), 269-280.
[http://dx.doi.org/10.1007/s10753-015-0247-5] [PMID: 26363638]
[15]
Devegowda, P.S.; Balaji, K.S.; Prasanna, D.S.; Swaroop, T.R.; Jayarama, S.; Siddalingaiah, L.; Rangappa, K.S. Pro-apoptotic activity of novel 4-anilinoquinazoline derivatives mediated by up-regulation of bax and activation of poly(ADP)ribose phosphatase in ehrlich ascites carcinoma cells. Asian J. Chem., 2017, 29(4), 896-904.
[http://dx.doi.org/10.14233/ajchem.2017.20356]
[16]
Preethi, S.D.; Balaji, K.S.; Prasanna, D.S.; Swaroop, T.R.; Shankar, J.; Rangappa, K.S.; Lokesh, S. Synthesis, characterization of 4-anilino-6,7-dimethoxyquinazoline derivatives as potential anti-angionic agents. Anticancer. Agents Med. Chem., 2017, 17(14), 1931-1941.
[17]
Abdel-Wahab, S.M.; Abdelsamii, Z.K.; Abdel-Fattah, H.A.; El-Etrawy, A.S.; Dawe, L.N.; Swaroop, T.R.; Georghiou, P.E. Synthesis of 2-aryl- and 2-haloarylbenzimidazole-N1-acetamido conjugates and a preliminary evaluation of their antifungal properties. ChemistrySelect, 2018, 3(28), 8106-8110.
[http://dx.doi.org/10.1002/slct.201801151]
[18]
Anil, S.M.; Rajeev, N.; Kiran, K.R.; Swaroop, T.R.; Mallesha, N.; Shobith, R.; Sadashiva, M.P. Multi-pharmacophore approach to bio-therapeutics: piperazine derived pseudo-peptidic urea/thiourea derivatives as anti-oxidant agents. Int. J. Pept. Res. Ther., 2020, 26(1), 151-158.
[http://dx.doi.org/10.1007/s10989-019-09824-4]
[19]
Narasimhamurthy, K.H.; Chandra; Swaroop, T.R.; Jagadish, S.; Rangappa, K.S. Synthesis of piperidine conjugated dihydroquinazolin-4(1H)-ones and their antiproliferative activity, molecular docking studies and DFT calculations. Lett. Drug Des. Discov., 2019, 17(1), 85-93.
[http://dx.doi.org/10.2174/1570180816666190613120349]
[20]
Chavva, K.; Pillalamarri, S.; Banda, V.; Gautham, S.; Gaddamedi, J.; Yedla, P.; Kumar, C.G.; Banda, N. Synthesis and biological evaluation of novel alkyl amide functionalized trifluoromethyl substituted pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents. Bioorg. Med. Chem. Lett., 2013, 23(21), 5893-5895.
[http://dx.doi.org/10.1016/j.bmcl.2013.08.089] [PMID: 24060486]
[21]
Kurumurthy, C.; Veeraswamy, B.; Sambasiva, R.P.; Santhosh, K.G.; Shanthan, R.P.; Loka, R.V.; Venkateswara, R.J.; Narsaiah, B. Synthesis of novel 1,2,3-triazole tagged pyrazolo[3,4-b]pyridine derivatives and their cytotoxic activity. Bioorg. Med. Chem. Lett., 2014, 24(3), 746-749.
[http://dx.doi.org/10.1016/j.bmcl.2013.12.107] [PMID: 24424132]
[22]
Nagender, P.; Naresh Kumar, R.; Malla Reddy, G.; Krishna Swaroop, D.; Poornachandra, Y.; Ganesh Kumar, C.; Narsaiah, B. Synthesis of novel hydrazone and azole functionalized pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents. Bioorg. Med. Chem. Lett., 2016, 26(18), 4427-4432.
[http://dx.doi.org/10.1016/j.bmcl.2016.08.006] [PMID: 27528432]
[23]
Salem, M.S.; Ali, M.A.M. Novel pyrazolo[3,4-b]pyridine derivatives: Synthesis, characterization, antimicrobial and antiproliferative profile. Biol. Pharm. Bull., 2016, 39(4), 473-483.
[http://dx.doi.org/10.1248/bpb.b15-00586] [PMID: 27040621]
[24]
Eissa, I.H.; El-Naggar, A.M.; El-Hashash, M.A. Design, synthesis, molecular modeling and biological evaluation of novel 1H-pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents. Bioorg. Chem., 2016, 67, 43-56.
[http://dx.doi.org/10.1016/j.bioorg.2016.05.006] [PMID: 27253830]
[25]
Jian, X.E.; Yang, F.; Jiang, C.S.; You, W.W.; Zhao, P.L. Synthesis and biological evaluation of novel pyrazolo[3,4-b]pyridines as cis-restricted combretastatin A-4 analogues. Bioorg. Med. Chem. Lett., 2020, 30(8), 127025-127025.
[http://dx.doi.org/10.1016/j.bmcl.2020.127025] [PMID: 32063430]
[26]
Bisagni, E.; Pepin, O.; Pierre, A.; De Cointet, P.; de Cointet, P. 1-Amino-substituted 4-methyl-5H-pyrido[3′,4′:4,5]pyrrolo[3,2-c]pyridines: A new class of antineoplastic agents. J. Med. Chem., 1987, 30(9), 1642-1647.
[http://dx.doi.org/10.1021/jm00392a021] [PMID: 3625709]
[27]
Jung, M.H.; El-Gamal, M.I.; Abdel-Maksoud, M.S.; Sim, T.; Yoo, K.H.; Oh, C.H. Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines. Part 2. Bioorg. Med. Chem. Lett., 2012, 22(13), 4362-4367.
[http://dx.doi.org/10.1016/j.bmcl.2012.05.004] [PMID: 22647720]
[28]
Carbone, A.; Pennati, M.; Parrino, B.; Lopergolo, A.; Barraja, P.; Montalbano, A.; Spanò, V.; Sbarra, S.; Doldi, V.; De Cesare, M.; Cirrincione, G.; Diana, P.; Zaffaroni, N. Novel 1H-pyrrolo[2,3-b]pyridine derivative nortopsentin analogues: synthesis and antitumor activity in peritoneal mesothelioma experimental models. J. Med. Chem., 2013, 56(17), 7060-7072.
[http://dx.doi.org/10.1021/jm400842x] [PMID: 23919303]
[29]
Narva, S.; Chitti, S.; Bala, B.R.; Alvala, M.; Jain, N.; Kondapalli, V.G.C.S. Synthesis and biological evaluation of pyrrolo[2,3- b]pyridine analogues as antiproliferative agents and their interaction with calf thymus DNA. Eur. J. Med. Chem., 2016, 114, 220-231.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.059] [PMID: 26994690]
[30]
Elansary, A.K.; Moneer, A.A.; Kadry, H.H.; Gedawy, E.M. Synthesis and anticancer activity of some novel fused pyridine ring system. Arch. Pharm. Res., 2012, 35(11), 1909-1917.
[http://dx.doi.org/10.1007/s12272-012-1107-6] [PMID: 23212632]
[31]
Romagnoli, R.; Baraldi, P.G.; Kimatrai Salvador, M.; Preti, D.; Aghazadeh Tabrizi, M.; Bassetto, M.; Brancale, A.; Hamel, E.; Castagliuolo, I.; Bortolozzi, R.; Basso, G.; Viola, G. Synthesis and biological evaluation of 2-(alkoxycarbonyl)-3-anilinobenzo[b]thiophenes and thieno[2,3-b]pyridines as new potent anticancer agents. J. Med. Chem., 2013, 56(6), 2606-2618.
[http://dx.doi.org/10.1021/jm400043d] [PMID: 23445496]
[32]
Zafar, A.; Sari, S.; Leung, E.; Pilkington, L.; van Rensburg, M.; Barker, D.; Reynisson, J. GPCR modulation of thieno[2,3-b]pyridine anti-proliferative agents. Molecules, 2017, 22(12), 2254-2254.
[http://dx.doi.org/10.3390/molecules22122254] [PMID: 29258235]
[33]
Naresh Kumar, R.; Poornachandra, Y.; Nagender, P.; Mallareddy, G.; Ravi Kumar, N.; Ranjithreddy, P.; Ganesh Kumar, C.; Narsaiah, B. Synthesis of novel trifluoromethyl substituted furo[2,3- b]pyridine and pyrido[3′,2′:4,5]furo[3,2- d]pyrimidine derivatives as potential anticancer agents. Eur. J. Med. Chem., 2016, 108, 68-78.
[http://dx.doi.org/10.1016/j.ejmech.2015.11.007] [PMID: 26629861]
[34]
Park, S.; Thapa Magar, T.B.; Kadayat, T.M.; Lee, H.J.; Bist, G.; Shrestha, A.; Lee, E.S.; Kwon, Y. Rational design, synthesis, and evaluation of novel 2,4-Chloro- and Hydroxy-Substituted diphenyl Benzofuro[3,2-b]Pyridines: Non-intercalative catalytic topoisomerase I and II dual inhibitor. Eur. J. Med. Chem., 2017, 127, 318-333.
[http://dx.doi.org/10.1016/j.ejmech.2017.01.003] [PMID: 28068603]
[35]
Santhosh Kumar, G.; Poornachandra, Y.; Kumar Gunda, S.; Ratnakar Reddy, K.; Mohmed, J.; Shaik, K.; Ganesh, K.C.; Narsaiah, B. Synthesis of novel hetero ring fused pyridine derivatives; Their anticancer activity, CoMFA and CoMSIA studies. Bioorg. Med. Chem. Lett., 2018, 28(13), 2328-2337.
[http://dx.doi.org/10.1016/j.bmcl.2018.04.031] [PMID: 29798826]
[36]
Sanghai, N.; Jain, V.; Preet, R.; Kandekar, S.; Das, S.; Trivedi, N.; Mohapatra, P.; Priyadarshani, G.; Kashyap, M.; Das, D.; Satapathy, S.R.; Siddharth, S.; Guchhait, S.K.; Kundu, C.N.; Bharatam, P.V. Combretastatin A-4 inspired novel 2-aryl-3-arylamino-imidazo-pyridines/pyrazines as tubulin polymerization inhibitors, antimitotic and anticancer agents. Med. Chem. Comm., 2014, 5(6), 766-782.
[http://dx.doi.org/10.1039/C3MD00357D]
[37]
An, W.; Wang, W.; Yu, T.; Zhang, Y.; Miao, Z.; Meng, T.; Shen, J. Discovery of novel 2-phenyl-imidazo[1,2-a]pyridine analogues targeting tubulin polymerization as antiproliferative agents. Eur. J. Med. Chem., 2016, 112, 367-372.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.004] [PMID: 26927488]
[38]
Fan, Y.H.; Li, W.; Liu, D.D.; Bai, M.X.; Song, H.R.; Xu, Y.N.; Lee, S.; Zhou, Z.P.; Wang, J.; Ding, H.W. Design, synthesis, and biological evaluation of novel 3-substituted imidazo[1,2- a]pyridine and quinazolin-4(3H)-one derivatives as PI3Kα inhibitors. Eur. J. Med. Chem., 2017, 139, 95-106.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.074] [PMID: 28800461]
[39]
Vasu, K.K.; Digwal, C.S.; Pandya, A.N.; Pandya, D.H.; Sharma, J.A.; Patel, S.; Agarwal, M. Imidazo[1,2- a]pyridines linked with thiazoles/thiophene motif through keto spacer as potential cytotoxic agents and NF-κB inhibitors. Bioorg. Med. Chem. Lett., 2017, 27(24), 5463-5466.
[http://dx.doi.org/10.1016/j.bmcl.2017.10.060] [PMID: 29138027]
[40]
Ramya, P.V.S.; Guntuku, L.; Angapelly, S.; Digwal, C.S.; Lakshmi, U.J.; Sigalapalli, D.K.; Babu, B.N.; Naidu, V.G.M.; Kamal, A. Synthesis and biological evaluation of curcumin inspired imidazo[1,2-a]pyridine analogues as tubulin polymerization inhibitors. Eur. J. Med. Chem., 2018, 143, 216-231.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.010] [PMID: 29174816]
[41]
Chitti, S.; Singireddi, S.; Santosh, K.R.P.; Trivedi, P.; Bobde, Y.; Kumar, C.; Rangan, K.; Ghosh, B.; Sekhar, K.V.G.C. Design, synthesis and biological evaluation of 2-(3,4-dimethoxyphenyl)-6 (1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-a]pyridine analogues as antiproliferative agents. Bioorg. Med. Chem. Lett., 2019, 29(18), 2551-2558.
[http://dx.doi.org/10.1016/j.bmcl.2019.08.013] [PMID: 31420269]
[42]
Meenakshisundaram, S.; Manickam, M.; Pillaiyar, T. Exploration of imidazole and imidazopyridine dimers as anticancer agents: Design, synthesis, and structure–activity relationship study. Arch. Pharm., 2019, 352(12), 1900011.
[http://dx.doi.org/10.1002/ardp.201900011] [PMID: 31596021]
[43]
Kamal, A.; Ramakrishna, G.; Ramaiah, M.J.; Viswanath, A.; Rao, A.V.S.; Bagul, C.; Mukhopadyay, D.; Pushpavalli, S.N.C.V.L.; Pal-Bhadra, M. Design, synthesis and biological evaluation of imidazo[1,5-a]pyridine–PBD conjugates as potential DNA-directed alkylating agents. Med. Chem. Comm., 2013, 4(4), 697-703.
[http://dx.doi.org/10.1039/c2md20219k]
[44]
Kamal, A.; Reddy, J.S.; Ramaiah, M.J.; Dastagiri, D.; Bharathi, E.V.; Prem Sagar, M.V.; Pushpavalli, S.N.C.V.L.; Ray, P.; Pal-Bhadra, M. Design, synthesis and biological evaluation of imidazopyridine/pyrimidine-chalcone derivatives as potential anticancer agents. Med. Chem. Comm., 2010, 1(5), 355-360.
[http://dx.doi.org/10.1039/c0md00116c]
[45]
Temple, C., Jr; Rose, J.D.; Comber, R.N.; Rener, G.A. Synthesis of potential anticancer agents: Imidazo[4,5-c]pyridines and imidazo[4,5-b]pyridines. J. Med. Chem., 1987, 30(10), 1746-1751.
[http://dx.doi.org/10.1021/jm00393a011] [PMID: 3656351]
[46]
Sajith, A.M.; Abdul Khader, K.K.; Joshi, N.; Reddy, M.N.; Syed, A.P.M.; Nagaswarupa, H.P.; Nibin, J.M.; Bodke, Y.D.; Karuvalam, R.P.; Banerjee, R.; Muralidharan, A.; Rajendra, P. Design, synthesis and structure–activity relationship (SAR) studies of imidazo[4,5-b]pyridine derived purine isosteres and their potential as cytotoxic agents. Eur. J. Med. Chem., 2015, 89, 21-31.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.037] [PMID: 25462222]
[47]
Marie, K.E.; Batra, T.; Karthikeyan, C.; Deora, G.S.; Rathore, V.; Mulakayala, C.; Mulakayala, N.; Nusbaum, A.C.; Chen, J.; Amawi, H.; McIntosh, K.; Sahabjada; Shivnath, N.; Chowarsia, D.; Sharma, N.; Arshad, M.; Trivedi, P.; Tiwari, A.K. 2,3-Diaryl-3 H -imidazo[4,5- b]pyridine derivatives as potential anticancer and anti-inflammatory agents. Acta Pharm. Sin. B, 2017, 7(1), 73-79.
[http://dx.doi.org/10.1016/j.apsb.2016.05.003] [PMID: 28119811]
[48]
Ghanem, N.M.; Farouk, F.; George, R.F.; Abbas, S.E.S.; El-Badry, O.M. Design and synthesis of novel imidazo[4,5-b]pyridine based compounds as potent anticancer agents with CDK9 inhibitory activity. Bioorg. Chem., 2018, 80, 565-576.
[http://dx.doi.org/10.1016/j.bioorg.2018.07.006] [PMID: 30025343]
[49]
Hwang, D.J.; Wang, J.; Li, W.; Miller, D.D. Structural optimization of indole derivatives acting at colchicine binding site as potential anticancer agents. ACS Med. Chem. Lett., 2015, 6(9), 993-997.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00208] [PMID: 26396686]
[50]
Gu, L.; Jin, C. Synthesis and antitumor activity of α-aminophosphonates containing thiazole[5,4-b]pyridine moiety. Org. Biomol. Chem., 2012, 10(35), 7098-7102.
[http://dx.doi.org/10.1039/c2ob25875g] [PMID: 22850968]
[51]
Kadayat, T.M.; Song, C.; Kwon, Y.; Lee, E.S. Modified 2,4-diaryl-5H-indeno[1,2-b]pyridines with hydroxyl and chlorine moiety: Synthesis, anticancer activity, and structure–activity relationship study. Bioorg. Chem., 2015, 62, 30-40.
[http://dx.doi.org/10.1016/j.bioorg.2015.07.002] [PMID: 26218799]