Advancements in Pyrazine Derivatives as Anticancer Agents: A Comprehensive Review (2010-2024)
- Авторы: Alshahrani M.1
-
Учреждения:
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University
- Выпуск: Том 25, № 3 (2025)
- Страницы: 151-163
- Раздел: Oncology
- URL: https://kld-journal.fedlab.ru/1871-5206/article/view/694480
- DOI: https://doi.org/10.2174/0118715206333399240912071555
- ID: 694480
Цитировать
Полный текст
Аннотация
Cancer, an intricate and formidable disease, continues to challenge Medical Science with its diverse manifestations and relentless progression. In the pursuit of novel therapeutic strategies, organic heterocyclic compounds have emerged as promising candidates due to their versatile chemical structures and intricate interactions with biological systems. Among these, pyrazine derivatives are characterized by a six-membered aromatic ring containing four carbon and two nitrogen atoms situated in a 1,4-orientation. These compounds garnered significant attention for their potential as anticancer agents. This comprehensive review provides a detailed analysis of the advancements made during this timeframe, encompassing the chemical diversity of pyrazine derivatives, their mechanisms of action at the cellular level, and structure-activity relationships, spanning the years 2010 to 2024. By examining their therapeutic potential, challenges, and future prospects, this review offers valuable insights into the evolving landscape of pyrazine derivatives as potent tools in the fight against cancer.
Ключевые слова
Об авторах
Mohammed Alshahrani
Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University
Автор, ответственный за переписку.
Email: info@benthamscience.net
Список литературы
- Mustafa, M.; Abbas, K.; Alam, M.; Ahmad, W.; Moinuddin, U.N.; Siddiqui, S.A.; Habib, S. Molecular pathways and therapeutic targets linked to triple-negative breast cancer (TNBC). Mol. Cell. Biochem., 2023, 20232023, 1-19. doi: 10.1007/s11010-023-04772-6 PMID: 37247161
- Alharbi, F.; Vakanski, A. Machine learning methods for cancer classification using gene expression data: A review. Bioengineering (Basel), 2023, 10(2), 173. doi: 10.3390/bioengineering10020173
- Fontana, A. Unravelling the nexus: Towards a unified model of development, ageing, and cancer. Biosystems, 2023, 231, 104966. doi: 10.1016/j.biosystems.2023.104966 PMID: 37419274
- Masoudi, R.; Gopalan, V. Cancer stem cells in cancer initiation and progression. In: Cancer Stem Cells: Basic Concept and Therapeutic Implications; Springer: Singapore, 2023; pp. 119-133. doi: 10.1007/978-981-99-3185-9_7
- Kirkland, J.L. Tumor dormancy and disease recurrence. Cancer Metastasis Rev., 2023, 42(1), 9-12. doi: 10.1007/s10555-023-10096-0 PMID: 36877312
- Singh, A.K.; Singh, S.V.; Kumar, R.; Kumar, S.; Senapati, S.; Pandey, A.K. Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise. World J. Hepatol., 2023, 15(1), 1-18. doi: 10.4254/wjh.v15.i1.1 PMID: 36744169
- Wang, Q.; Shao, X.; Zhang, Y.; Zhu, M.; Wang, F.X.C.; Mu, J.; Li, J.; Yao, H.; Chen, K. Role of tumor microenvironment in cancer progression and therapeutic strategy. Cancer Med., 2023, 12(10), 11149-11165. doi: 10.1002/cam4.5698 PMID: 36807772
- Mohammad Abu-Taweel, G.; Alharthi, S.S.; Al-Saidi, H.M.; Babalghith, A.O.; Ibrahim, M.M.; Khan, S. Heterocyclic organic compounds as a fluorescent chemosensor for cell imaging applications: A review. Crit. Rev. Anal. Chem., 2023, 1-16. doi: 10.1080/10408347.2023.2186695 PMID: 36880659
- Alrooqi, M.; Khan, S.; Alhumaydhi, F.A.; Asiri, S.A.; Alshamrani, M.; Mashraqi, M.M.; Alzamami, A.; Alshahrani, A.M.; Aldahish, A.A. A therapeutic journey of pyridine-based heterocyclic compounds as potent anticancer agents: A review (from 2017 to 2021). Anticancer. Agents Med. Chem., 2022, 22(15), 2775-2787. doi: 10.2174/1871520622666220324102849 PMID: 35331100
- Khan, S.; Alhumaydhi, F.A.; Ibrahim, M.M.; Alqahtani, A.; Alshamrani, M.; Alruwaili, A.S.; Hassanian, A.A.; Khan, S. Recent advances and therapeutic journey of schiff base complexes with selected metals (Pt, Pd, Ag, Au) as potent anticancer agents: A review. Anticancer. Agents Med. Chem., 2022, 22(18), 3086-3096. doi: 10.2174/1871520622666220511125600 PMID: 35546764
- Mohammad Abu-Taweel, G.; Ibrahim, M.M.; Khan, S.; Al-Saidi, H.M.; Alshamrani, M.; Alhumaydhi, F.A.; Alharthi, S.S. Medicinal importance and chemosensing applications of pyridine derivatives: A review. Crit. Rev. Anal. Chem., 2024, 54(3), 599-616. doi: 10.1080/10408347.2022.2089839 PMID: 35724248
- Abdullah Al Awadh, A. Biomedical applications of selective metal complexes of indole, benzimidazole, benzothiazole and benzoxazole: A review (From 2015 to 2022). Saudi Pharm. J., 2023, 31(9), 101698. doi: 10.1016/j.jsps.2023.101698 PMID: 37533494
- Baranwal, J.; Kushwaha, S.; Singh, S.; Jyoti, A. A review on the synthesis and pharmacological activity of heterocyclic compounds. Curr. Phys. Chem., 2023, 13(1), 2-19. doi: 10.2174/1877946813666221021144829
- Khan, S.; Muhammad, M.; Al-Saidi, H.M.; Hassanian, A.A.; Alharbi, W.; Alharbi, K.H. Synthesis, characterization and applications of schiff base chemosensor for determination of Cu2+ ions. J. Saudi Chem. Soc., 2022, 26(4), 101503. doi: 10.1016/j.jscs.2022.101503
- Al-Saidi, H.M.; Khan, S. A review on organic fluorimetric and colorimetric chemosensors for the detection of Ag(I) ions. Crit. Rev. Anal. Chem., 2022, 54(6), 1810-1836. doi: 10.1080/10408347.2022.2133561 PMID: 36251012
- Alhamami, M.A.M.; Algethami, J.S.; Khan, S. A review on thiazole based colorimetric and fluorimetric chemosensors for the detection of heavy metal ions. Crit. Rev. Anal. Chem., 2023, 1-25. doi: 10.1080/10408347.2023.2197073 PMID: 37029905
- Al-Saidi, H.M.; Khan, S. Recent advances in thiourea based colorimetric and fluorescent chemosensors for detection of anions and neutral analytes: A review. Crit. Rev. Anal. Chem., 2022, 54(1), 93-109. doi: 10.1080/10408347.2022.2063017
- Khan, S.; Chen, X.; Almahri, A.; Allehyani, E.S.; Alhumaydhi, F.A.; Ibrahim, M.M.; Ali, S. Recent developments in fluorescent and colorimetric chemosensors based on schiff bases for metallic cations detection: A review. J. Environ. Chem. Eng., 2021, 9(6), 106381. doi: 10.1016/j.jece.2021.106381
- Hou, W.; Dai, W.; Huang, H.; Liu, S.L.; Liu, J.; Huang, L.J.; Huang, X.H.; Zeng, J.L.; Gan, Z.W.; Zhang, Z.Y.; Lan, J.X. Pharmacological activity and mechanism of pyrazines. Eur. J. Med. Chem., 2023, 258, 115544. doi: 10.1016/j.ejmech.2023.115544 PMID: 37300915
- Choudhary, D.; Garg, S.; Kaur, M.; Sohal, H.S.; Malhi, D.S.; Kaur, L.; Verma, M.; Sharma, A.; Mutreja, V. Advances in the synthesis and bio-applications of pyrazine derivatives: A review. Polycycl. Aromat. Compd., 2022, 43(5), 4512-4578. doi: 10.1080/10406638.2022.2092873
- Goel, R.; Luxami, V.; Paul, K. Synthesis, in vitro anticancer activity and SAR studies of arylated imidazo1,2-apyrazine–coumarin hybrids. RSC Advances, 2015, 5(47), 37887-37895. doi: 10.1039/C5RA00584A
- Andrejević, T.P.; Aleksic, I.; Kljun, J.; Počkaj, M.; Zlatar, M.; Vojnovic, S.; Nikodinovic-Runic, J.; Turel, I.; Djuran, M.I.; Glišić, B.Đ. Copper(ii) and silver(i) complexes with dimethyl 6-(pyrazine-2-yl)pyridine-3,4-dicarboxylate (py-2pz): The influence of the metal ion on the antimicrobial potential of the complex. RSC Advances, 2023, 13(7), 4376-4393. doi: 10.1039/D2RA07401J PMID: 36744286
- Foks, H.; Pancechowska-Ksepko, D.; Kędzia, A.; Zwolska, Z.; Janowiec, M.; Augustynowicz-Kopeć, E. Synthesis and antibacterial activity of 1H-pyrazolo3,4-bpyrazine and -pyridine derivatives. Farmaco, 2005, 60(6-7), 513-517. doi: 10.1016/j.farmac.2005.05.002 PMID: 15950227
- Gobis, K.; Foks, H.; Kędzia, A.; Wierzbowska, M.; Zwolska, Z. Synthesis and antibacterial activity of novel pyridine and pyrazine derivatives obtained from amidoximes. J. Heterocycl. Chem., 2009, 46(6), 1271-1279. doi: 10.1002/jhet.251
- El-Kashef, H.; El-Emary, T.; Verhaeghe, P.; Vanelle, P.; Samy, M. Anticancer and anti-inflammatory activities of some new pyrazolo3,4- bpyrazines. Molecules, 2018, 23(10), 2657. doi: 10.3390/molecules23102657
- Silva, Y.K.C.; Augusto, C.V.; Barbosa, M.L.C.; Melo, G.M.A.; Queiroz, A.C.; Dias, T.L.M.F.; Júnior, W.B.; Barreiro, E.J.; Lima, L.M.; Alexandre-Moreira, M.S. Synthesis and pharmacological evaluation of pyrazine N-acylhydrazone derivatives designed as novel analgesic and anti-inflammatory drug candidates. Bioorg. Med. Chem., 2010, 18(14), 5007-5015. doi: 10.1016/j.bmc.2010.06.002 PMID: 20598893
- Zaki, R.M.; Kamal El-Dean, A.M.; Radwan, S.M. Abd ul-Malik, M.a. A convenient synthesis, reactions and biological activities of some novel thieno3,2-epyrazolo3,4-bpyrazine compounds as anti-microbial and anti-inflammatory agents. Curr. Org. Synth., 2018, 15, 863-871. doi: 10.2174/1570179415666180607105627
- Kucerova-Chlupacova, M.; Dosedel, M.; Kunes, J.; Soltesova-Prnova, M.; Majekova, M.; Stefek, M. Chalcones and their pyrazine analogs: Synthesis, inhibition of aldose reductase, antioxidant activity, and molecular docking study. Monatsh. Chem., 2018, 149(5), 921-929. doi: 10.1007/s00706-018-2146-6
- Stepanić, V.; Matijašić, M.; Horvat, T.; Verbanac, D.; Chlupáćová, M.K.; Saso, L.; Žarković, N. Antioxidant activities of alkyl substituted pyrazine derivatives of chalcones — In vitro and in silico study. Antioxidants, 2019, 8(4), 90. doi: 10.3390/antiox8040090
- Dolezal, M.; Zitko, J. Pyrazine derivatives: A patent review (June 2012 – present). Expert Opin. Ther. Pat., 2014, 25(1), 33-47. doi: 10.1517/13543776.2014.982533
- Ferreira, S.B.; Kaiser, C.R. Pyrazine derivatives: A patent review (2008 – present). Expert Opin. Ther. Pat., 2012, 22(9), 1033-1051. doi: 10.1517/13543776.2012.714370
- Tambat, N.; Mulani, S.K.; Ahmad, A.; Shaikh, S.B.; Ahmed, K. Pyrazine derivatives—versatile scaffold. Russ. J. Bioorg. Chem., 2022, 48(5), 865-895. doi: 10.1134/S1068162022050259
- Huigens, R.W.; Brummel, B.R.; Tenneti, S.; Garrison, A.T.; Xiao, T. Pyrazine and phenazine heterocycles: Platforms for total synthesis and drug discovery. Molecules, 2022, 27(3), 1112. doi: 10.3390/molecules27031112
- Hodoň, J.; Frydrych, I.; Trhlíková, Z.; Pokorný, J.; Borková, L.; Benická, S.; Vlk, M.; Lišková, B.; Kubíčková, A.; Medvedíková, M.; Pisár, M.; Šarek, J.; Das, V.; Ligasová, A.; Koberna, K.; Džubák, P.; Hajdúch, M.; Urban, M. Triterpenoid pyrazines and pyridines – Synthesis, cytotoxicity, mechanism of action, preparation of prodrugs. Eur. J. Med. Chem., 2022, 243, 114777. doi: 10.1016/j.ejmech.2022.114777 PMID: 36174412
- Myadaraboina, S.; Alla, M.; Saddanapu, V.; Bommena, V.R.; Addlagatta, A. Structure activity relationship studies of imidazo1,2-apyrazine derivatives against cancer cell lines. Eur. J. Med. Chem., 2010, 45(11), 5208-5216. doi: 10.1016/j.ejmech.2010.08.035 PMID: 20832916
- Kékesi, L.; Sipos, A.; Németh, G.; Pató, J.; Breza, N.; Baska, F.; Őrfi, L.; Kéri, G. Synthesis and biological evaluation of novel pyrido2,3-bpyrazines inhibiting both erlotinib-sensitive and erlotinib-resistant cell lines. Bioorg. Med. Chem. Lett., 2013, 23(22), 6152-6155. doi: 10.1016/j.bmcl.2013.09.005 PMID: 24095095
- 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. MedChemComm, 2014, 5(6), 766-782. doi: 10.1039/C3MD00357D
- Zhang, H.; Wang, Y.; Zhu, P.; Liu, J.; Xu, S.; Yao, H.; Jiang, J.; Ye, W.; Wu, X.; Xu, J. Design, synthesis and antitumor activity of triterpenoid pyrazine derivatives from 23-hydroxybetulinic acid. Eur. J. Med. Chem., 2015, 97, 235-244. doi: 10.1016/j.ejmech.2015.04.057 PMID: 25984840
- Lalitha, P.; Veena, V.; Vidhyapriya, P.; Lakshmi, P.; Krishna, R.; Sakthivel, N. anticancer potential of pyrrole (1, 2, a) pyrazine 1, 4, dione, hexahydro 3-(2-methyl propyl) (ppdhmp) extracted from a new marine bacterium, staphylococcus sp. strain mb30. Apoptosis, 2016, 21(5), 566-577. doi: 10.1007/s10495-016-1221-x PMID: 26852140
- Argyros, O.; Lougiakis, N.; Kouvari, E.; Papafotika, A.; Raptopoulou, C.P.; Psycharis, V.; Christoforidis, S.; Pouli, N.; Marakos, P.; Tamvakopoulos, C. Design and synthesis of novel 7-aminosubstituted pyrido2,3-bpyrazines exhibiting anti-breast cancer activity. Eur. J. Med. Chem., 2017, 126, 954-968. doi: 10.1016/j.ejmech.2016.12.025 PMID: 28006668
- Fang, K.; Zhang, X.H.; Han, Y.T.; Wu, G.R.; Cai, D.S.; Xue, N.N.; Guo, W.B.; Yang, Y.Q.; Chen, M.; Zhang, X.Y. Design, synthesis, and cytotoxic analysis of novel hederagenin–pyrazine derivatives based on partial least squares discriminant analysis. Int. J. Mol. Sci., 2018, 19(10), 2994. doi: 10.3390/ijms19102994
- Patil, S.R.; Sarkate, A.P.; Karnik, K.S.; Arsondkar, A.; Patil, V.; Sangshetti, J.N.; Bobade, A.S.; Shinde, D.B. A facile synthesis of substituted 2‐(5‐(benzylthio)‐1,3,4‐oxadiazol‐2‐yl)pyrazine using microwave irradiation and conventional method with antioxidant and anticancer activities. J. Heterocycl. Chem., 2019, 56(3), 859-866. doi: 10.1002/jhet.3464
- Li, Y.; Wei, X.; Bai, S.; Xu, Z.G.; Lv, M. One‐pot synthesis of benzimidazole‐pyrazines and their anticancer activities. J. Heterocycl. Chem., 2019, 56(12), 3429-3434. doi: 10.1002/jhet.3701
- Singh, I.; Luxami, V.; Paul, K. Effective synthesis of benzimidazoles-imidazo1,2-apyrazine conjugates: A comparative study of mono-and bis-benzimidazoles for antitumor activity. Eur. J. Med. Chem., 2019, 180, 546-561. doi: 10.1016/j.ejmech.2019.07.042 PMID: 31344614
- De Wang, X.; Li, T.; Li, Y.; Yuan, W.H.; Zhao, Y.Q. 2-Pyrazine-PPD, a novel dammarane derivative, showed anticancer activity by reactive oxygen species-mediate apoptosis and endoplasmic reticulum stress in gastric cancer cells. Eur. J. Pharmacol., 2020, 881, 173211. doi: 10.1016/j.ejphar.2020.173211 PMID: 32464194
- Wang, S.; Yuan, X.; Qian, H.; Li, N.; Wang, J. Design, synthesis, and biological evaluation of two series of novel a-ring fused steroidal pyrazines as potential anticancer agents. Int. J. Mol. Sci., 2020, 21(5), 1665. doi: 10.3390/ijms21051665
- Zaki, R.M.; Abdul-Malik, M.A.; Saber, S.H.; Radwan, S.M.; El-Dean, A.M.K. A convenient synthesis, reactions and biological evaluation of novel pyrazolo3,4-bselenolo3,2-epyrazine heterocycles as potential anticancer and antimicrobial agents. Med. Chem. Res., 2020, 29(12), 2130-2145. doi: 10.1007/s00044-020-02635-z
- 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. doi: 10.1016/j.molstruc.2020.128013
- Rodrigues, J.M.; Calhelha, R.C.; Nogueira, A.; Ferreira, I.C.F.R.; Barros, L.; Queiroz, M.J.R.P. Synthesis of novel methyl 7-(hetero)arylaminothieno2,3-bpyrazine-6-carboxylates and antitumor activity evaluation: Effects in human tumor cells growth, cell cycle analysis, apoptosis and toxicity in non-tumor cells. Molecule, 2021, 26(16), 4823. doi: 10.3390/molecules26164823
- Ghoneim, A.A.; Ali Hassan, A.G. An efficient procedure of synthesis acyclic c-glycosides of thiazolo4,5-bpyrazine and imidazo4,5-dthiazole with expected anti-cancer activities. 2020, 46(6), 3328-3338. doi: 10.1080/10406638.2020.1866035
- Rachala, M.R.; Maringanti, T.C.; Syed, T.; Eppakayala, L. Synthesis and biological evaluation of 1,3,4-oxadiazole bearing pyrimidine-pyrazine derivatives as anticancer agents. Synth. Commun., 2023, 53(15), 1262-1268. doi: 10.1080/00397911.2023.2219354
Дополнительные файлы
