User:Sufangxi/沙盒
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| 臨床資料 | |
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| CAS号 | 34524-20-4  |
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| 化学信息 | |
| 化学式 | C45H74BNO15 |
| 摩尔质量 | 879.89 g·mol−1 |
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硼霉素（英語：Boromycin）是最早从抗生素链霉菌（Streptomyces antibioticus）中分离出的一种聚醚-大环内酯抗生素，亦是发现的首个含硼元素的天然产物。可抗大多数革兰氏阳性菌，对革兰氏阴性菌无效。对钾离子有亲和性，由此引起细菌胞内钾离子流失，膜电位迅速紊乱失衡，生长停滞、细胞质蛋白泄漏最终使细胞死亡[1]。目前尚未批准用于临床药物[2]。
发现历史
硼霉素由苏黎世联邦理工学院的学者在研究微生物的代谢产物过程中发现，并将其研究成果于1967年发表在《瑞士化学学报》上[3]。他们在科特迪瓦贝乌米省土壤中发现的新抗生素链霉菌菌株上发现其能产生一种含有硼元素的新奇抗生素，并命名为“boromycin”。鉴定其结构，发现其为一种由硼酸与有机四齿配体组成的螯合物。水解后产生D-缬氨酸、硼酸以及一个多羟基大环内酯[3][4]。
用途
硼霉素具有许多潜在的医疗用途，可用作革兰氏阳性细菌感染、球虫和某些原虫感染的抗生素，但其临床有效性和安全性尚未确定[4]，目前尚未批准用于临床药物[2]。对革兰氏阳性有抗菌活性，对阴性菌和真菌无效。除此之外，对疟原虫属以及巴倍虫属两种原生动物也有抑制活性[4]。
It has been predicted to inhibit the replication of HIV-1[6] and the synthesis of proteins, RNA, and DNA in whole cells of Bacillus subtilis. Boromycin binds to the cytoplasmic membrane within the cell and is antagonized by surface-active compounds. It is bound to lipoprotein and does not influence the K+, Na+-ATPase of the cytoplasmic membrane.[4]
The removal of boric acid from the boromycin molecule leads to a loss of antibiotic activity. There are minor products of boromycin fermentation, differing in the acylation position. Experiments with feeding the production strain Sorangium cellulosum with specific isotopes have shed light on the biosynthesis of tartrolons, which are closely related to boromycin and aplasmomycin.[4]
Research
Boron, the essential trace element found in boromycin, benefits plants, animals, and humans. Boron-containing compounds such as boromycin have gained attention for their potential medicinal applications.[4]
Anti-HIV activity
A 1996 study suggests that boromycin has anti-HIV activity in in vitro laboratory experiments. In that study, boromycin inhibited the replication of both clinically isolated HIV-1 strains and cultured strains. The mechanism of action was believed to involve blocking the later stage of HIV infection, specifically the maturity step for replication of the HIV molecule.[6]
While the study provides promising results in a controlled laboratory setting, it is important to note that in vitro experiments do not always accurately predict the effectiveness of a compound in living organisms. Strong evidence should be accumulated to determine boromycin's actual in vivo anti-HIV activity in a living human organism. Accumulating such evidence typically involves preclinical studies in animal models to assess safety, efficacy, and pharmacokinetics before progressing to clinical trials in humans.[7][8]
The lack of replication of the 1996 study's[6] findings by other studies suggests a lack of confirmation regarding the anti-HIV activity of boromycin. This could be due to potential methodological limitations in the original study, such as variations in experimental conditions or difficulties in isolating and purifying boromycin. It is also possible that the initial study produced a false positive result, where the observed anti-HIV activity resulted from chance or experimental artifacts rather than a true effect. Additionally, publication bias may play a role, as positive or novel findings are more likely to be published, potentially leading to an incomplete picture of the overall research on boromycin's anti-HIV activity. Studies are needed to address these factors and determine the true effectiveness of boromycin as an in vivo anti-HIV agent.[9][10][11][12]
Anti-plasmodium activity
In a 2021 study,[13] boromycin showed activity against Plasmodium falciparum and Plasmodium knowlesi, two species of malaria parasites. It demonstrated rapid killing of asexual stages of both species, including multidrug-resistant strains, at low concentrations. Additionally, boromycin exhibited activity against Plasmodium falciparum stage V gametocytes. However, other studies have not confirmed these results and should be interpreted cautiously. Additional scientific investigation and validation are required to establish the efficacy of boromycin as a potential antimalarial candidate. It is essential to conduct further studies to confirm and substantiate the findings, ensuring reliable and reproducible results. The potential of boromycin in the context of malaria treatment warrants continued research and rigorous examination to assess its effectiveness and potential implications for therapeutic applications fully.[14]
Activity against intracellular protozoal parasites
A 2021 study[5] by scholars from Central Luzon State University, Philippines, and Washington State University, USA, showed the activity of boromycin against Toxoplasma gondii and Cryptosporidium parvum, which are intracellular protozoal parasites affecting humans and animals. The study found that boromycin effectively inhibited the intracellular proliferation of both parasites at low concentrations. However, these preliminary results have not yet been confirmed by further studies. To validate the results and understand the potential of boromycin as a therapeutic option for the treatment of toxoplasmosis and cryptosporidiosis, it is critical to conduct studies to confirm the activity of boromycin against intracellular protozoan parasites in living host organisms.[5]
References
- ^ Jaypee Abenoja, Alexis Cotto-Rosario, Roberta O’Connor. Boromycin Has Potent Anti-Toxoplasma and Anti-Cryptosporidium Activity. Antimicrobial Agents and Chemotherapy. 2021, 65 (4): e01278-20. doi:10.1128/aac.01278-20.
- ^ 2.0 2.1 Jessica Plescia, Nicolas Moitessier. Design and discovery of boronic acid drugs. European Journal of Medicinal Chemistry. 2020, 195 (1): 112270. doi:10.1016/j.ejmech.2020.112270.
- ^ 3.0 3.1 Hütter R, Keller-Schierlein W, Knüsel F, Prelog V, Rodgers GC, Suter P, et al. [The metabolic products of microorganisms. Boromycin]. Helvetica Chimica Acta. January 1967, 50 (6): 1533–1539. PMID 6081908. doi:10.1002/hlca.19670500612.
- ^ 4.0 4.1 4.2 4.3 4.4 4.5 Rezanka T, Sigler K. Biologically active compounds of semi-metals. Phytochemistry. February 2008, 69 (3): 585–606. Bibcode:2008PChem..69..585R. PMID 17991498. doi:10.1016/j.phytochem.2007.09.018.
- ^ 5.0 5.1 5.2 Abenoja J, Cotto-Rosario A, O'Connor R. Boromycin Has Potent Anti-Toxoplasma and Anti-Cryptosporidium Activity. Antimicrobial Agents and Chemotherapy. March 2021, 65 (4). PMC 8097477
. PMID 33468470. doi:10.1128/AAC.01278-20.
- ^ 6.0 6.1 6.2 Kohno J, Kawahata T, Otake T, Morimoto M, Mori H, Ueba N, et al. Boromycin, an anti-HIV antibiotic. Bioscience, Biotechnology, and Biochemistry. June 1996, 60 (6): 1036–1037. PMID 8695905. doi:10.1271/bbb.60.1036 .
- ^ Chien JY, Friedrich S, Heathman MA, de Alwis DP, Sinha V. Pharmacokinetics/Pharmacodynamics and the stages of drug development: role of modeling and simulation. The AAPS Journal. October 2005, 7 (3): E544–E559. PMC 2751257 . PMID 16353932. doi:10.1208/aapsj070355.
- ^ Mead S, Tagliavini F. Clinical trials. Human Prion Diseases. Handbook of Clinical Neurology 153. Elsevier. 2018: 431–444. ISBN 9780444639455. PMID 29887150. doi:10.1016/B978-0-444-63945-5.00024-6.
- ^ Mehta M, Schug B, Blume HH, Beuerle G, Jiang W, Koenig J, et al. The Global Bioequivalence Harmonisation Initiative (GBHI): Report of the fifth international EUFEPS/AAPS conference. European Journal of Pharmaceutical Sciences. November 2023, 190: 106566. PMID 37591469. S2CID 260943533. doi:10.1016/j.ejps.2023.106566 .
- ^ Lee J, Gong Y, Bhoopathy S, DiLiberti CE, Hooker AC, Rostami-Hodjegan A, et al. Public Workshop Summary Report on Fiscal Year 2021 Generic Drug Regulatory Science Initiatives: Data Analysis and Model-Based Bioequivalence. Clinical Pharmacology and Therapeutics. November 2021, 110 (5): 1190–1195. PMID 33236362. S2CID 227165142. doi:10.1002/cpt.2120.
- ^ Pepin XJ, Dressman J, Parrott N, Delvadia P, Mitra A, Zhang X, et al. In Vitro Biopredictive Methods: A Workshop Summary Report. Journal of Pharmaceutical Sciences. February 2021, 110 (2): 567–583. PMID 32956678. S2CID 221842404. doi:10.1016/j.xphs.2020.09.021 .
- ^ Kitaeva KV, Rutland CS, Rizvanov AA, Solovyeva VV. Cell Culture Based in vitro Test Systems for Anticancer Drug Screening. Frontiers in Bioengineering and Biotechnology. 2020, 8: 322. PMC 7160228 . PMID 32328489. doi:10.3389/fbioe.2020.00322 .
- ^ de Carvalho LP, Groeger-Otero S, Kreidenweiss A, Kremsner PG, Mordmüller B, Held J. Boromycin has Rapid-Onset Antibiotic Activity Against Asexual and Sexual Blood Stages of Plasmodium falciparum. Frontiers in Cellular and Infection Microbiology. 2021, 11: 802294. PMC 8795978 . PMID 35096650. doi:10.3389/fcimb.2021.802294 .
- ^ Kumar V, Bhargava G. Editorial: Protozoal infections: Treatment and challenges. Frontiers in Cellular and Infection Microbiology. 2022, 12: 1002602. PMC 9471550 . PMID 36118046. doi:10.3389/fcimb.2022.1002602 .
