Design, Synthesis, and Biological Evaluation of Novel Thiazolidinone-Containing Quinoxaline-1,4-di--oxides As Antimycobacterial and Antifungal Agents

Overview

Journal Front Chem

Specialty Chemistry

Date 2020 Aug 28

PMID 32850634

Citations 8

Authors

Heying Zhang

Jie Zhang

Wei Qu

Shuyu Xie

Lingli Huang

Dongmei Chen

Yanfei Tao

Zhenli Liu

Yuanhu Pan

Zonghui Yuan

Affiliations

Soon will be listed here.

Abstract

Tuberculosis and fungal infections can pose serious threats to human health. In order to find novel antimicrobial agents, 26 novel quinoxaline-1,4-di--oxides containing a thiazolidinone moiety were designed and synthesized, and their antimycobacterial activities were evaluated. Among them, compounds , , , and displayed the most potent antimycobacterial activity against strain H37Rv (minimal inhibitory concentration [MIC] = 1.56 μg/mL). The antifungal activity of all the compounds was also evaluated against , and . Compounds , , , and exhibited potential antifungal activities, with an MIC between 2 and 4 μg/mL. Comparative molecular field analysis (CoMFA: = 0.914, = 0.967) and comparative molecular similarity index analysis (CoMSIA: = 0.918, = 0.968) models were established to investigate the structure and antimycobacterial activity relationship. The results of contour maps revealed that electronegative and sterically bulky substituents play an important role in the antimycobacterial activity. Electronegative and sterically bulky substituents are preferred at the C7 position of the quinoxaline ring and the C4 position of the phenyl group to increase the antimycobacterial activity. Additionally, more hydrogen bond donor substituents should be considered at the C2 side chain of the quinoxaline ring to improve the activity.

Citing Articles

Synthesis, crystal structure and Hirshfeld surface analysis of 1-[(1-octyl-1-1,2,3-triazol-4-yl)methyl]-3-phenyl-1,2-di-hydro-quinoxalin-2(1)-one.

Abad N, Mague J, Kalonji Mubengayi C, Alsubari A, Essassi E, Ramli Y Acta Crystallogr E Crystallogr Commun. 2024; 80(Pt 9):936-941.

PMID: 39267873 PMC: 11389679. DOI: 10.1107/S2056989024007746.

Expanding the chemical space of ester of quinoxaline-7-carboxylate 1,4-di--oxide derivatives as potential antitubercular agents.

Gonzalez-Gonzalez A, Sanchez-Sanchez O, Wan B, Franzblau S, Palos I, Espinoza-Hicks J RSC Med Chem. 2024; 15(8):2785-2791.

PMID: 39149106 PMC: 11324059. DOI: 10.1039/d4md00221k.

Quinoxaline 1,4-Dioxides: Advances in Chemistry and Chemotherapeutic Drug Development.

Buravchenko G, Shchekotikhin A Pharmaceuticals (Basel). 2023; 16(8).

PMID: 37631089 PMC: 10459860. DOI: 10.3390/ph16081174.

Synthesis, In Silico and Pharmacological Evaluation of New Thiazolidine-4-Carboxylic Acid Derivatives Against Ethanol-Induced Neurodegeneration and Memory Impairment.

Naz S, Al Kury L, Nadeem H, Shah F, Ullah A, Paracha R J Inflamm Res. 2022; 15:3643-3660.

PMID: 35783245 PMC: 9241999. DOI: 10.2147/JIR.S357082.

The Bioactivity of Thiazolidin-4-Ones: A Short Review of the Most Recent Studies.

Mech D, Kurowska A, Trotsko N Int J Mol Sci. 2021; 22(21).

PMID: 34768964 PMC: 8584074. DOI: 10.3390/ijms222111533.

References

Villar R, Vicente E, Solano B, Perez-Silanes S, Aldana I, Maddry J . In vitro and in vivo antimycobacterial activities of ketone and amide derivatives of quinoxaline 1,4-di-N-oxide. J Antimicrob Chemother. 2008; 62(3):547-54. PMC: 2574959. DOI: 10.1093/jac/dkn214. View

Jiang Z, Gu J, Wang C, Wang S, Liu N, Jiang Y . Design, synthesis and antifungal activity of novel triazole derivatives containing substituted 1,2,3-triazole-piperdine side chains. Eur J Med Chem. 2014; 82:490-7. DOI: 10.1016/j.ejmech.2014.05.079. View

Skinner P, Furney S, Jacobs M, Klopman G, Ellner J, Orme I . A bone marrow-derived murine macrophage model for evaluating efficacy of antimycobacterial drugs under relevant physiological conditions. Antimicrob Agents Chemother. 1994; 38(11):2557-63. PMC: 188241. DOI: 10.1128/AAC.38.11.2557. View

Rajule R, Bryant V, Lopez H, Luo X, Natarajan A . Perturbing pro-survival proteins using quinoxaline derivatives: a structure-activity relationship study. Bioorg Med Chem. 2012; 20(7):2227-34. PMC: 3303926. DOI: 10.1016/j.bmc.2012.02.022. View

Glaziou P, Floyd K, Raviglione M . Global Epidemiology of Tuberculosis. Semin Respir Crit Care Med. 2018; 39(3):271-285. DOI: 10.1055/s-0038-1651492. View

Wise R . The urgent need for new antibacterial agents. J Antimicrob Chemother. 2011; 66(9):1939-40. DOI: 10.1093/jac/dkr261. View

Zhao S, Zhang X, Wei P, Su X, Zhao L, Wu M . Design, synthesis and evaluation of aromatic heterocyclic derivatives as potent antifungal agents. Eur J Med Chem. 2017; 137:96-107. DOI: 10.1016/j.ejmech.2017.05.043. View

Carta A, Piras S, Loriga G, Paglietti G . Chemistry, biological properties and SAR analysis of quinoxalinones. Mini Rev Med Chem. 2006; 6(11):1179-200. DOI: 10.2174/138955706778742713. View

Ancizu S, Moreno E, Solano B, Villar R, Burguete A, Torres E . New 3-methylquinoxaline-2-carboxamide 1,4-di-N-oxide derivatives as anti-Mycobacterium tuberculosis agents. Bioorg Med Chem. 2010; 18(7):2713-9. DOI: 10.1016/j.bmc.2010.02.024. View

10.

Keri R, Pandule S, Budagumpi S, Nagaraja B . Quinoxaline and quinoxaline-1,4-di-N-oxides: An emerging class of antimycobacterials. Arch Pharm (Weinheim). 2018; 351(5):e1700325. DOI: 10.1002/ardp.201700325. View

11.

Zarranz B, Jaso A, Aldana I, Monge A, Maurel S, Deharo E . Synthesis and antimalarial activity of new 3-arylquinoxaline-2-carbonitrile derivatives. Arzneimittelforschung. 2006; 55(12):754-61. DOI: 10.1055/s-0031-1296926. View

12.

Ortega M, Sainz Y, Montoya M, Jaso A, Zarranz B, Aldana I . Anti-Mycobacterium tuberculosis agents derived from quinoxaline-2-carbonitrile and quinoxaline-2-carbonitrile 1,4-di-N-oxide. Arzneimittelforschung. 2002; 52(2):113-9. DOI: 10.1055/s-0031-1299866. View

13.

Zhao J, Li Y, Hunt A, Zhang J, Yao H, Li Z . A Difluorobenzoxadiazole Building Block for Efficient Polymer Solar Cells. Adv Mater. 2015; 28(9):1868-73. DOI: 10.1002/adma.201504611. View

14.

Ortega M, Montoya M, Jaso A, Zarranz B, Tirapu I, Aldana I . Antimycobacterial activity of new quinoxaline-2-carbonitrile and quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives. Pharmazie. 2001; 56(3):205-7. View

15.

Brown G, Denning D, Gow N, Levitz S, Netea M, White T . Hidden killers: human fungal infections. Sci Transl Med. 2012; 4(165):165rv13. DOI: 10.1126/scitranslmed.3004404. View

16.

Ghareb N, Abdel Daim M, El-Sayed N, Elgawish M . Synthesis, molecular modelling, and preliminary anticonvulsant activity evaluation of novel naphthalen-2-yl acetate and 1,6-dithia-4,9-diazaspiro [4.4] nonane-3,8-dione derivatives. Bioorg Chem. 2017; 71:110-119. DOI: 10.1016/j.bioorg.2017.01.018. View

17.

Jimenez-Arellanes A, Meckes M, Ramirez R, Torres J, Luna-Herrera J . Activity against multidrug-resistant Mycobacterium tuberculosis in Mexican plants used to treat respiratory diseases. Phytother Res. 2003; 17(8):903-8. DOI: 10.1002/ptr.1377. View

18.

Palekar V, Damle A, Shukla S . Synthesis and antibacterial activity of some novel bis-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and bis-4-thiazolidinone derivatives from terephthalic dihydrazide. Eur J Med Chem. 2009; 44(12):5112-6. DOI: 10.1016/j.ejmech.2009.07.023. View

19.

Pan Y, Li P, Xie S, Tao Y, Chen D, Dai M . Synthesis, 3D-QSAR analysis and biological evaluation of quinoxaline 1,4-di-N-oxide derivatives as antituberculosis agents. Bioorg Med Chem Lett. 2016; 26(16):4146-53. DOI: 10.1016/j.bmcl.2016.01.066. View

20.

Wilhelmsson L, Kingi N, Bergman J . Interactions of antiviral indolo[2,3-b]quinoxaline derivatives with DNA. J Med Chem. 2008; 51(24):7744-50. DOI: 10.1021/jm800787b. View