摘要
背景：被忽视的热带病(NTDs)影响着世界上大量的人口，大多数受害者属于发展中国家的贫困社区。到目前为止，世界卫生组织(WHO)已确定20种热带疾病为非传染性疾病，必须予以高度优先处理。然而，许多杂环支架已经证明了对几种NTDs的有效治疗活性。 目的：有三个主要的目标:(1)讨论所有20种NTDs的原因、症状和现状;(2)探索治疗NTDs的现有杂环类药物及其作用机制(已知);(3)在医学/健康研究界及其他领域提高对NTDs的普遍认识。 方法：根据20种NTDs的字母顺序和可能的杂环药物进行了讨论。概述了目前以杂环药物(商用和研究)为主的治疗现状。此外，简要讨论了NTDs对社会经济条件的影响。 结果：NTDs通常很难诊断，发展中国家不健康的卫生、不恰当的认识和不充分的医疗保健使问题恶化，这些疾病主要影响穷人。统计数据包括痛苦的持续时间、受影响的人数以及获得保健和药物的机会。对已报道的各种杂环类药物的作用机制作了简要的综述。 结论：科学家和制药公司应该分配更多的资源来揭示目前用于治疗NTDs的许多杂环药物的深入作用机制。分析目前的杂环化合物和开发新药物有助于减少/消除NTDs的破坏性影响。提出了一项基于意见的简要审查。根据现有的文献，这是第一次尝试将所有20种NTDs和相关的杂环化合物放在同一伞下。
关键词: 被忽视的热带病(NTDs)、细菌、病毒、杂环、杂环药物、寄生虫、感染、感染
[1]
World Health Organization. Neglected Tropical Diseases, 2019. Available at: https://www.who.int/neglected_ diseases/mediacentre/factsheet/en/ (Accessed: 26 November, 2020).
[2]
Bandyopadhyay, D.; Banik, B.K. Microwave-induced synthesis of heterocycles of medicinal interests.In: Green Synthetic Approaches for Biologically Relevant Heterocycles; , 2015, 1, pp. 517-557.
[http://dx.doi.org/10.1016/B978-0-12-800070-0.00019-0]
[http://dx.doi.org/10.1016/B978-0-12-800070-0.00019-0]
[3]
World Health Organization. Buruli ulcer (Mycobacterium ulcerans infection) 2019. Available at: https://www. who.int/en/news-room/fact-sheets/detail/buruli-ulcer-(myco -bacterium-ulcerans-infection) (Accessed: 26 November, 2020).
[4]
Vadim, M.; Stewart, C. 2-piperazin-1-yl-4h-1,3-benzothiazin-4-one derivatives and their use for the treatment of mammalian infections. WO Patent (A1) 2,012,066,518, 2012.
[5]
Rassi, A., Jr; Rassi, A.; Marin-Neto, J.A. Chagas disease. Lancet, 2010, 375(9723), 1388-1402.
[http://dx.doi.org/10.1016/S0140-6736(10)60061-X] [PMID: 20399979]
[http://dx.doi.org/10.1016/S0140-6736(10)60061-X] [PMID: 20399979]
[6]
World Health Organization. Chagas disease (also known as American trypanosomiasis), 2020. Available at: https://www.who.int/en/news-room/fact-sheets/detail/chagas-disease(american-trypanosomiasis) (Accessed: 26 November, 2020).
[7]
Bernardes, L.S.C.; Zani, C.L.; Carvalho, I. Trypanosomatidae diseases: from the current therapy to the efficacious role of trypanothione reductase in drug discovery. Curr. Med. Chem., 2013, 20(21), 2673-2696.
[http://dx.doi.org/10.2174/0929867311320210005] [PMID: 23410156]
[http://dx.doi.org/10.2174/0929867311320210005] [PMID: 23410156]
[8]
Bandyopadhyay, D.; Samano, S.; Villalobos-Rocha, J.C.; Sanchez-Torres, L.E.; Nogueda-Torres, B.; Rivera, G.; Banik, B.K. A practical green synthesis, and biological
evaluation of benzimidazoles against tropical diseases: Chagas and Leishmaniasis. Curr. Med. Chem., 2017, 24(41), 4714-4725.
[http://dx.doi.org/10.2174/0929867325666171201101807] [PMID: 23317160]
[http://dx.doi.org/10.2174/0929867325666171201101807] [PMID: 23317160]
[9]
World Health Organization. Dengue and Severe Dengue, 2016. Available at: https://www.who.int/en/news-room/fact-sheets/detail/dengue-and-severe-dengue (Accessed: 26 November, 2020).
[11]
Asekunowo, P.O.; Haque, R.A.; Razali, M.R.; Avicor, S.W.; Wajidi, M.F.F. Synthesis and characterization of nitrile functionalized silver(I)-N-heterocyclic carbene complexes: DNA binding, cleavage studies, antibacterial properties and mosquitocidal activity against the dengue vector, Aedes albopictus. Eur. J. Med. Chem., 2018, 150, 601-615.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.029] [PMID: 29550733]
[http://dx.doi.org/10.1016/j.ejmech.2018.03.029] [PMID: 29550733]
[12]
World Health Organization. Dracunliasis 2018. Available at: https://www.who.int/dracunculiasis/en/ (Accessed: 26 November, 2020).
[13]
World Health Organization. Dracunculiasis (guinea-worm disease) 2020. Available at: https://www.who.int/en/news-room/fact-sheets/detail/dracunculiasis-(guinea-worm-disease) (Accessed: 26 November, 2020).
[14]
Linington, R.; Navarro, G.; Pudhom, K.; Mckerrow, J. Novel semi-synthetic small molecules for the treatment parasitic disease. WO Patent (A2) 2,013,019,686 2013.
[15]
World Health Organization. Echinococcosis 2020. Available at: https://www.who.int/echinococcosis/disease/en/ (Accessed: 26 November, 2020).
[16]
D’Alessandro, A.; Rausch, R.L. New aspects of neotropical polycystic (Echinococcus vogeli) and unicystic (Echinococcus oligarthrus) echinococcosis. Clin. Microbiol. Rev., 2008, 21(2), 380-401.
[http://dx.doi.org/10.1128/CMR.00050-07] [PMID: 18400802]
[http://dx.doi.org/10.1128/CMR.00050-07] [PMID: 18400802]
[17]
World Health Organization. Echinococcosis 2020. Available at: https://www.who.int/en/news-room/fact-sheets/detail/echinococcosis (Accessed: 26 November, 2020).
[18]
do Espirito Santo, R.D.; Machado, M.G.M.; dos Santos, J.L.; Gonzalez, E.R.P.; Chin, C.M. Use of guanidine compounds in the treatment of neglected tropical diseases. Curr. Org. Chem., 2014, 18, 2572-2602.
[http://dx.doi.org/10.2174/138527281820141028104429]
[http://dx.doi.org/10.2174/138527281820141028104429]
[19]
Zhang, H.; Liu, C.; Xue, J.; Duan, L.; Tao, Y.; Yao, J.; Wang, W.; Wei, Y.; Xu, L.; Zheng, Q.; Huo, L.; Tu, Z.; Zhao, Y.; Chen, Y.; Liu, N. Chinese medicinal composition
for treating tumor, ulcer and trauma hemorrhage on skin,
eczema, scabies, bromhidrosis, tinea pedis and onychomycosis and preparation method thereof. CN106,727,581A, 2017.
[20]
World Health Organization. Foodborne Trematodiases., Available at: https://www.who.int/en/news-room/fact-sheets/detail/foodborne-trematodiases (Accessed: 26 November, 2020).
[21]
Keiser, J.; Utzinger, J. Food-borne trematodiasis: current chemotherapy and advances with artemisinins and synthetic trioxolanes. Trends Parasitol., 2007, 23(11), 555-562.
[http://dx.doi.org/10.1016/j.pt.2007.07.012] [PMID: 17950667]
[http://dx.doi.org/10.1016/j.pt.2007.07.012] [PMID: 17950667]
[22]
Cayla, M.; Rojas, F.; Silvester, E.; Venter, F.; Matthews, K.R. African trypanosomes. Parasit. Vectors, 2019, 12(1), 190.
[http://dx.doi.org/10.1186/s13071-019-3355-5] [PMID: 31036044]
[http://dx.doi.org/10.1186/s13071-019-3355-5] [PMID: 31036044]
[23]
World Health Organization. Human African trypanosomiasis., Available at: https://www.who.int/trypanosomiasis_ african/disease/en/ (Accessed: 26 November, 2020).
[24]
Sutherland, C.S.; Tediosi, F. Is the elimination of ‘sleeping sickness’ affordable? Who will pay the price? Assessing the financial burden for the elimination of human African trypanosomiasis Trypanosoma brucei gambiense in sub-Saharan Africa. BMJ Glob. Health, 2019, 4(2)e001173
[http://dx.doi.org/10.1136/bmjgh-2018-001173] [PMID: 31139437]
[http://dx.doi.org/10.1136/bmjgh-2018-001173] [PMID: 31139437]
[25]
World Health Organization. Human African trypanosomiasis., Available at: https://www.who.int/trypanosomiasis_ african/news/progress-on-eliminating-hat-as-public-health-problem/en/ (Accessed: 26 November, 2020).
[26]
World Health Organization. Trypanosomiasis. Human
African (Sleeping Sickness) Available at: https://www. who.int/en/news-room/fact-sheets/detail/trypanosomiasis-human-african-(sleeping-sickness) (Accessed: 26 November, 2020).
[27]
Hiltensperger, G.; Jones, N.G.; Niedermeier, S.; Stich, A.; Kaiser, M.; Jung, J.; Puhl, S.; Damme, A.; Braunschweig, H.; Meinel, L.; Engstler, M.; Holzgrabe, U. Synthesis and structure-activity relationships of new quinolone-type molecules against Trypanosoma brucei. J. Med. Chem., 2012, 55(6), 2538-2548.
[http://dx.doi.org/10.1021/jm101439s] [PMID: 22376072]
[http://dx.doi.org/10.1021/jm101439s] [PMID: 22376072]
[28]
Winter, I.; Lockhauserbäumer, J.; Lallinger-Kube, G.; Schobert, R.; Ersfeld, K.; Biersack, B. Anti-trypanosomal activity of cationic N-heterocyclic carbene gold(I) complexes. Mol. Biochem. Parasitol., 2017, 214, 112-120.
[http://dx.doi.org/10.1016/j.molbiopara.2017.05.001] [PMID: 28522152]
[http://dx.doi.org/10.1016/j.molbiopara.2017.05.001] [PMID: 28522152]
[29]
World Health Organization. Leishmaniasis. Vector control Available at: https://www.who.int/leishmaniasis/vector-control/en/ (Accessed: 26 November, 2020).
[30]
World Health Organization. Leishmaniasis Available at: https://www.who.int/en/news-room/fact-sheets/detail/leishmaniasis (Accessed: 26 November, 2020).
[31]
World Health Organization. Report of a meeting of the WHO expert committee on the control of leishmaniases. WHO technical report series, 2010, 949, 54-73.
[32]
Dos Santos Fernandes, G.F.; Pavan, A.R.; Dos Santos, J.L. Heterocyclic N-oxides - a promising class of agents against tuberculosis, malaria and neglected tropical diseases. Curr. Pharm. Des., 2018, 24(12), 1325-1340.
[http://dx.doi.org/10.2174/1381612824666180417122625] [PMID: 29663875]
[http://dx.doi.org/10.2174/1381612824666180417122625] [PMID: 29663875]
[33]
National Institute of Allergy and Infectious Diseases. Leprosy (Hansen’s disease) 2015. Available at: https://www. niaid.nih.gov/diseases-conditions/leprosy-hansens-disease (Accessed: 26 November, 2020).
[34]
World Health Organization. Leprosy Available at: https://www.who.int/en/news-room/fact-sheets/detail-/leprosy (Accessed: 26 November, 2020).
[35]
Willand, N.; Deprez, B.; Baulard, A.; Brodin, P.; Flipo, M.; Maingot, L. Composes bicycliques ayant une activite potentialisatrice de l'activite d'un antibiotique actif contre les
mycobacteries-composition et produit pharmaceutiques
comprenant de tels composes F.R. Patent (A1) 3,000,065, 2014.
[36]
Centers of Disease Control and Prevention (USA). What is Hansen’s disease?, Available at: https://www.cdc.gov/lep-rosy/about/about.html (Accessed: 26 November, 2020).
[37]
World Health Organization. Lymphatic Filariasis., Available at: https://www.who.int/en/news-room/fact-sheets/de-tail/lymphatic-filariasis (Accessed: 26 November, 2020).
[38]
Centers of Disease Control and Prevention (USA). Parasites-Lymphatic Filariasis., Available at: https://www.cdc. gov/parasites/lymphaticfilariasis/treatment.html (Accessed: 26 November, 2020).
[39]
Mandvikar, A.; Hande, S.V.; Yeole, P.; Goswami, K.; Reddy, M.V.R. Therapeutic potential of novel heterocyclic thiazolidine compounds against human lymphatic filarial parasite: an in vitro study. Int. J. Pharm. Sci. Res., 2016, 7(4), 1480-1492.
[http://dx.doi.org/10.13040/IJPSR.0975-8232.]
[http://dx.doi.org/10.13040/IJPSR.0975-8232.]
[40]
World Health Organization. Neglected tropical diseases., Available at: https://www.who.int/neglected_diseases/-diseases/mycetoma-chromoblastomycosis-deep-mycoses/- en/index1.html (Accessed: 26 November, 2020).
[41]
World Health Organization. Mycetoma Available at: https://www.who.int/en/news-room/fact-sheets/detail/mycetoma (Accessed: 26 November, 2020).
[42]
Lu, H. Novel antifungal infection drugs as well as preparation method and applications thereof. CN Patent (A)
107,556,294 2018.
[43]
World Health Organization. Onchocerciasis Available at: https://www.who.int/en/news-room/fact-sheets/detail/onchocerciasis (Accessed: 26 November, 2020).
[44]
Centers of Disease Control and Prevention (USA). Parasites - Onchocerciasis (also known as River Blindness) Available at: https://www.cdc.gov/parasites/onchocercia-sis/treatment.html (Accessed: 26 November, 2020).
[45]
Centers of Disease Control and Prevention (USA). Onchocerciasis FAQs (also known as River Blindness) Available at: https://www.cdc.gov/parasites/onchocerciasis/gen_ info/faqs.html (Accessed: 26 November, 2020).
[46]
Chen, S.; Jiang, J.; Zhang, J.; Xie, Y. Benzoimidazolylpyrazine compounds for inflammation and immune-related
uses. U.S. Patent 6,043,045 2006.
[47]
Oloyede, G.K.; Onocha, P.A.; Oke, J.M. Mannich synthesis of 2-(thiazol-4-yl)-1H-benzimidazole-2-methylene piperazinyl (2,5-diamino-1,3,4-thiadiazolyl) oxamide and evaluation of the filaricidal activity. Am. Eur J. Sci. Res., 2011, 6(2), 116-122.
[48]
World Health Organization. Epidemiology and burden of disease., Available at: https://www.who.int/rabies/epide-miology/en/ (Accessed: 26 November, 2020).
[49]
World Health Organization. Rabies Available at: https://www.who.int/en/news-room/fact-sheets/detail/rabies (Accessed: 26 November, 2020).
[50]
Krogstad, P.; Jung, M.E.; Zuo, J.; Xing, Y. Potent antiviral
pyrazolopyridine compounds. WO Patent (A1)
2,017,053,604 2017.
[51]
Sasikumar, P.G.N.; Prasad, A.; Naremaddepalli, S.S.S.; Ramachandra, M. Cyclic substituted-1,3,4-oxadiazole and
thiadiazole compounds as immunomodulators. WO Patent
(A1) 2,018,051,255 2018.
[52]
World Health Organization. Rabies: Epidemiology and
burden of disease 2017. Available at: https://www.who. int/neglecteddiseases/diseases/scabies/en/ (Accessed: 26 November, 2020).
[53]
International Alliance for the Control of Scabies (IACS). Available at: http://www.controlscabies.org/ (Accessed: 26 November, 2020).
[54]
World Health Organization. Schistosomiasis Available at: https://www.who.int/en/news-room/fact-sheets/detail/schistosomiasis (Accessed: 26 November, 2020).
[55]
World Health Organization. Schistosomiasis. What is schistosomiasis? Available at: https://www.who.int/schisto-somiasis/disease/en/ (Accessed: 26 November, 2020).
[56]
de Brito, M.R.M.; Peláez, W.J.; Faillace, M.S.; Militão, G.C.G.; Almeida, J.R.G.S.; Argüello, G.A.; Szakonyi, Z.; Fülöp, F.; Salvadori, M.C.; Teixeira, F.S.; Freitas, R.M.; Pinto, P.L.S.; Mengarda, A.C.; Silva, M.P.N.; Da Silva Filho, A.A.; de Moraes, J. Cyclohexene-fused 1,3-oxazines with selective antibacterial and antiparasitic action and low cytotoxic effects. Toxicol. In Vitro, 2017, 44, 273-279.
[http://dx.doi.org/10.1016/j.tiv.2017.07.021] [PMID: 28755871]
[http://dx.doi.org/10.1016/j.tiv.2017.07.021] [PMID: 28755871]
[57]
World Health Organization. Neglected tropical diseases. Preventive chemotherapy for helminth diseases: progress
report 2014. Available at: https://www.who.int/neglected_ diseases/resources/who_wer9108/en/ (Accessed: 26 November, 2020).
[58]
World Health Organization. Soil Transmitted Helminth Infections., Available at: https://www.who.int/en/news-room/fact-sheets/detail/soil-transmitted-helminth-infections (Accessed: 26 November, 2020).
[59]
Balaji, P.N.; Ranganayakulu, D.; Reddy, G.V.S. Synthesis, in vitro evaluation for anthelmintic and antimicrobial activity for the novel thiazolidine-4-one incorporate substituted chloro-quinoline. Asian J. Pharm. Pharmacol., 2017, 3(1), 9-15.
[60]
Husain, A.; Varshney, M.M.; Parcha, V.; Ahmad, A.; Khan, S.A. Nalidixic acid Schiff bases: synthesis and biological evaluation. Lett. Drug Des. Discov., 2018, 15, 103-111.
[http://dx.doi.org/10.2174/1570180814666170710160751]
[http://dx.doi.org/10.2174/1570180814666170710160751]
[61]
World Health Organization. Snakebite Envenoming., Available at: https://www.who.int/en/news-room/fact-sheets/detail/snakebite-envenoming (Accessed: 26 November, 2020).
[62]
Slade, H.B. Method for the treatment of dermal lesions
caused by envenomation. WO Patent (A2) 0,174,343 2010.
[63]
Centers of Disease Control and Prevention (USA). Parasites - Taeniasis Available at: https://www.cdc.gov/-parasites/taeniasis/index.html (Accessed: 26 November, 2020).
[64]
World Health Organization. Taeniasis Available at: https://www.who.int/taeniasis/disease/en/ (Accessed: 26 November, 2020).
[65]
World Health Organization. Taeniasis/Cysticercosis. Available at: https://www.who.int/en/news-room/fact-sheets/detail/taeniasis-cysticercosis (Accessed: 26 November, 2020).
[66]
Centers of Disease Control and Prevention (USA). Parasites-Taeniasis: Treatment Available at: https://www.cdc. gov/parasites/taeniasis/treatment.html (Accessed: 26 November, 2020).
[67]
Centers of Disease Control and Prevention (USA). Hygiene-related Diseases., Available at: https://www.cdc.gov/healthywater/hygiene/disease/trachoma.html (Accessed: 26 November, 2020).
[68]
World Health Organization. Trachoma 2017. Available at: https://www.who.int/en/news-room/fact-sheets/detail/trachoma (Accessed: 26 November, 2020).
[69]
Finn, P.W.; Charlton, M.; Edmund, G.; Jirgensons, A.; Loza, E. 2-amino-N-(arylsulfinyl)-acetamide compounds as
inhibitors of bacterial aminoacyl-tRNA synthetase. WO
Patent (A1) 2,018,065,611 2019.
[70]
Werner, M.H.; Kelly, T.A. Compositions and methods for
inhibiting kinases. WO Patent (A1) 2,016,172,528 2016.
[71]
Emerson, P.M.; Ngondi, J. Mass antibiotic treatment alone does not eliminate ocular chlamydial infection. PLoS Negl. Trop. Dis., 2009, 3(3)e394
[http://dx.doi.org/10.1371/journal.pntd.0000394] [PMID: 19333370]
[http://dx.doi.org/10.1371/journal.pntd.0000394] [PMID: 19333370]
[72]
World Health Organization. Neglected tropical diseases. Accelerating yaws eradication: antibiotic added to WHO’s
essential medicines list. , Available at: https://www. who.int/neglected_diseases/news/accelerating_yaws_eradication/en/ (Accessed: 26 November, 2020).
[73]
World Health Organization. Yaws 2012. Available at: http://www.who.int/en/news-room/fact-sheets/detail/yaws (Accessed: 26 November, 2020).
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