使用者:Sufangxi/沙盒
 | |
| 臨床資料 | |
|---|---|
| ATC碼 |
|
| 識別資訊 | |
| |
| CAS號 | 34524-20-4  |
| PubChem CID | |
| ChemSpider | |
| UNII | |
| ChEBI | |
| 化學資訊 | |
| 化學式 | C45H74BNO15 |
| 摩爾質量 | 879.89 g·mol−1 |
| 3D模型（JSmol） | |
| |
| |
硼黴素（英語：Boromycin）是最早從抗生素鏈黴菌（Streptomyces antibioticus）中分離出的一種聚醚-大環內酯抗生素，亦是發現的首個含硼元素的天然產物。可抗大多數革蘭氏陽性菌，對革蘭氏陰性菌無效。對鉀離子有親和性，由此引起細菌胞內鉀離子流失，膜電位迅速紊亂失衡，生長停滯、細胞質蛋白洩漏最終使細胞死亡[1]。目前尚未批准用於臨床藥物[2]。
發現歷史
硼黴素由蘇黎世聯邦理工學院的學者在研究微生物的代謝產物過程中發現，並將其研究成果於1967年發表在《瑞士化學學報》上[3]。他們在象牙海岸貝烏米省土壤中發現的新抗生素鏈黴菌菌株上發現其能產生一種含有硼元素的新奇抗生素，並命名為「boromycin」。鑑定其結構，發現其為一種由硼酸與有機四齒配體組成的螯合物。水解後產生D-纈氨酸、硼酸以及一個多羥基大環內酯[3][4]。
用途
硼黴素具有許多潛在的醫療用途，可用作革蘭氏陽性細菌感染、球蟲和某些原蟲感染的抗生素，但其臨床有效性和安全性尚未確定[4]，目前尚未批准用於臨床藥物[2]。對革蘭氏陽性有抗菌活性，對陰性菌和真菌無效。除此之外，對瘧原蟲屬以及巴倍蟲屬兩種原生動物也有抑制活性[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 .
