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'''Boromycin''' is a bacteriocidal [[polyether]]-[[macrolide]] [[antibiotic]]. It was initially isolated from the ''[[Streptomyces antibioticus]]'', and is notable for being the first natural product found to contain the element [[boron]]. It is effective against most [[Gram-positive]] bacteria, but is ineffective against [[Gram-negative]] bacteria. Boromycin kills bacteria by negatively affecting the cytoplasmic membrane, resulting in the loss of [[potassium]] ions from the cell.
'''Boromycin''' is a bacteriocidal [[polyether]]-[[macrolide]] [[antibiotic]]. It was initially isolated from the ''[[Streptomyces antibioticus]]'', and is notable for being the first natural product found to contain the element [[boron]]. It is effective against most [[Gram-positive]] bacteria, but is ineffective against [[Gram-negative]] bacteria. Boromycin kills bacteria by negatively affecting the cytoplasmic membrane, resulting in the loss of [[potassium]] ions from the cell.


==Research==
==Anti-HIV activity==
===Anti-HIV activity===
Recent studies have suggested that boromycin has potent anti-HIV activity. It was found to strongly inhibit the replication of the clinically isolated HIV-1 [[strain (biology)|strain]] as well as the cultured strain [[in vitro]]. The [[mechanism of action]] for the anti-HIV activity of boromycin is suggested to involve interfering with the later stage of HIV infection, and possibly the maturation step for the replication of HIV.
A 1996 study suggests that boromycin has anti-HIV activity in vitro laboratory experiments. In that study, it 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.<ref name="pmid8695905">{{cite journal |vauthors=Kohno J, Kawahata T, Otake T, Morimoto M, Mori H, Ueba N, Nishio M, Kinumaki A, Komatsubara S, Kawashima K |title=Boromycin, an anti-HIV antibiotic |journal=Biosci Biotechnol Biochem |volume=60 |issue=6 |pages=1036–7 |date=June 1996 |pmid=8695905 |doi=10.1271/bbb.60.1036 |url=}}</ref>

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.<ref name="pmid16353932">{{cite journal |vauthors=Chien JY, Friedrich S, Heathman MA, de Alwis DP, Sinha V |title=Pharmacokinetics/Pharmacodynamics and the stages of drug development: role of modeling and simulation |journal=AAPS J |volume=7 |issue=3 |pages=E544–59 |date=October 2005 |pmid=16353932 |pmc=2751257 |doi=10.1208/aapsj070355 |url=}}</ref>
<ref name="pmid29887150">{{cite book |vauthors=Mead S, Tagliavini F |title=Human Prion Diseases |chapter=Clinical trials |journal=Handb Clin Neurol |series=Handbook of Clinical Neurology |volume=153 |issue= |pages=431–444 |date=2018 |pmid=29887150 |doi=10.1016/B978-0-444-63945-5.00024-6 |isbn=9780444639455 |url=}}</ref>

The lack of replication of the 1996 study's<ref name="pmid8695905"/> 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. Further research is necessary to address these factors and determine the true effectiveness of boromycin as an in-vivo anti-HIV agent.<ref name="pmid37591469">{{cite journal |vauthors=Mehta M, Schug B, Blume HH, Beuerle G, Jiang W, Koenig J, Paixao P, Tampal N, Tsang YC, Walstab J, Wedemeyer R, Welink J |title=The Global Bioequivalence Harmonisation Initiative (GBHI): Report of the fifth international EUFEPS/AAPS conference |journal=Eur J Pharm Sci |volume=190 |issue= |pages=106566 |date=November 2023 |pmid=37591469 |doi=10.1016/j.ejps.2023.106566 |s2cid=260943533 |url=}}</ref><ref name="pmid33236362">{{cite journal |vauthors=Lee J, Gong Y, Bhoopathy S, DiLiberti CE, Hooker AC, Rostami-Hodjegan A, Schmidt S, Suarez-Sharp S, Lukacova V, Fang L, Zhao L |title=Public Workshop Summary Report on Fiscal Year 2021 Generic Drug Regulatory Science Initiatives: Data Analysis and Model-Based Bioequivalence |journal=Clin Pharmacol Ther |volume=110 |issue=5 |pages=1190–1195 |date=November 2021 |pmid=33236362 |doi=10.1002/cpt.2120 |s2cid=227165142 |url=http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-431954}}</ref><ref name="pmid32956678">{{cite journal |vauthors=Pepin XJH, Dressman J, Parrott N, Delvadia P, Mitra A, Zhang X, Babiskin A, Kolhatkar V, Seo P, Taylor LS, Sjögren E, Butler JM, Kostewicz E, Tannergren C, Koziolek M, Kesisoglou F, Dallmann A, Zhao Y, Suarez-Sharp S |title=In Vitro Biopredictive Methods: A Workshop Summary Report |journal=J Pharm Sci |volume=110 |issue=2 |pages=567–583 |date=February 2021 |pmid=32956678 |doi=10.1016/j.xphs.2020.09.021 |s2cid=221842404 |url=}}</ref><ref name="pmid32328489">{{cite journal |vauthors=Kitaeva KV, Rutland CS, Rizvanov AA, Solovyeva VV |title=Cell Culture Based in vitro Test Systems for Anticancer Drug Screening |journal=Front Bioeng Biotechnol |volume=8 |issue= |pages=322 |date=2020 |pmid=32328489 |pmc=7160228 |doi=10.3389/fbioe.2020.00322 |url= |doi-access=free }}</ref>

=== Anti-plasmodium activity ==
In a 2021 study,<ref name="pmid35096650">{{cite journal |vauthors=de Carvalho LP, Groeger-Otero S, Kreidenweiss A, Kremsner PG, Mordmüller B, Held J |title=Boromycin has Rapid-Onset Antibiotic Activity Against Asexual and Sexual Blood Stages of Plasmodium falciparum |journal=Front Cell Infect Microbiol |volume=11 |issue= |pages=802294 |date=2021 |pmid=35096650 |pmc=8795978 |doi=10.3389/fcimb.2021.802294 |url= |doi-access=free }}</ref> boromycin showed activity of boromycin 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 P. 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.<ref name="pmid36118046">{{cite journal |vauthors=Kumar V, Bhargava G |title=Editorial: Protozoal infections: Treatment and challenges |journal=Front Cell Infect Microbiol |volume=12 |issue= |pages=1002602 |date=2022 |pmid=36118046 |pmc=9471550 |doi=10.3389/fcimb.2022.1002602 |url= |doi-access=free }}</ref>

===Activity against intracellular protozoal parasites===
A 2021 study<ref name="pmid33468470"/> 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, it is important to note that these results are preliminary and have not been confirmed by further studies. To validate the findings and understand the potential of boromycin as a therapeutic option for treating toxoplasmosis and cryptosporidiosis, it is crucial to conduct further studies to confirm boromycin's activity against intracellular protozoal parasites in living organisms.<ref name="pmid33468470">{{cite journal |vauthors=Abenoja J, Cotto-Rosario A, O'Connor R |title=Boromycin Has Potent Anti-Toxoplasma and Anti-Cryptosporidium Activity |journal=Antimicrob Agents Chemother |volume=65 |issue=4 |pages= |date=March 2021 |pmid=33468470 |pmc=8097477 |doi=10.1128/AAC.01278-20 |url=}}</ref>


== References ==
== References ==

Revision as of 21:24, 16 October 2023

Boromycin
Clinical data
ATC code
  • none
Identifiers
  • [1-{(1R)-1-[(1R,2R,5S,6R,8R,12R,14S,17R,18R,22S,24Z,28S,30S,33R)-12,28-Dihydroxy-1,2,18,19-tetra(hydroxy-κO)-6,13,13,17,29,29,33-heptamethyl-3,20-dioxo-4,7,21,34,35-pentaoxatetracyclo[28.3.1.15,8.114,18]hexatriacont-24-en-22-yl]ethoxy}-3-methyl-1-oxo-2-butanaminiumato(4-)]boron
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC45H74BNO15
Molar mass879.89 g·mol−1
3D model (JSmol)
  • CC(C)C([NH3+])C(=O)O[C@H](C)[C@H]7OC(=O)C4O[B-]25O[C@@H](C(=O)O[C@H]1C[C@H](O[C@@H]1C)CCC[C@@H](O)C(C)(C)[C@@H]3CC[C@@H](C)[C@@]4(O2)O3)[C@]6(O5)O[C@@H](CC[C@H]6C)C(C)(C)[C@@H](O)CC\C=C/C7
  • InChI=1S/C45H73BNO15/c1-24(2)36(47)39(50)54-27(5)30-16-12-11-13-17-32(48)42(7,8)34-21-19-26(4)45(57-34)38-41(52)56-31-23-29(53-28(31)6)15-14-18-33(49)43(9,10)35-22-20-25(3)44(58-35)37(40(51)55-30)59-46(60-38,61-44)62-45/h11-12,24-38,48-49H,13-23,47H2,1-10H3/q-1/p+1/b12-11-/t25-,26-,27-,28-,29-,30+,31+,32+,33-,34+,35+,36?,37?,38+,44+,45+,46?/m1/s1 checkY
  • Key:OOBFYEMEQCZLJL-WIHWYPJVSA-O checkY
 ☒NcheckY (what is this?)  (verify)

Boromycin is a bacteriocidal polyether-macrolide antibiotic. It was initially isolated from the Streptomyces antibioticus, and is notable for being the first natural product found to contain the element boron. It is effective against most Gram-positive bacteria, but is ineffective against Gram-negative bacteria. Boromycin kills bacteria by negatively affecting the cytoplasmic membrane, resulting in the loss of potassium ions from the cell.

Research

Anti-HIV activity

A 1996 study suggests that boromycin has anti-HIV activity in vitro laboratory experiments. In that study, it 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.[1]

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.[2] [3]

The lack of replication of the 1996 study's[1] 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. Further research is necessary to address these factors and determine the true effectiveness of boromycin as an in-vivo anti-HIV agent.[4][5][6][7]

= Anti-plasmodium activity

In a 2021 study,[8] boromycin showed activity of boromycin 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 P. 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.[9]

Activity against intracellular protozoal parasites

A 2021 study[10] 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, it is important to note that these results are preliminary and have not been confirmed by further studies. To validate the findings and understand the potential of boromycin as a therapeutic option for treating toxoplasmosis and cryptosporidiosis, it is crucial to conduct further studies to confirm boromycin's activity against intracellular protozoal parasites in living organisms.[10]

References

  • Kohno J, Kawahata T, Otake T, Morimoto M, Mori H, Ueba N, Nishio M, Kinumaki A, Komatsubara S, Kawashima K (1996). "Boromycin, an anti-HIV antibiotic". Biosci Biotechnol Biochem. 60 (6): 1036–7. doi:10.1271/bbb.60.1036. PMID 8695905.
  • Tom S. S. Chen; Ching-jer Chang & Heinz G. Floss (1981). "On the Biosynthesis of Boromycin". Journal of Organic Chemistry. 46 (13): 2661–2665. doi:10.1021/jo00326a010.
  • R. Hütter; W. Keller-Schien; F. Knüsel; V. Prelog; G. C. Rodgers Jr.; P. Suter; G. Vogel; W. Voser; H. Zähner (1967). "Stoffwechselprodukte von Mikroorganismen. 57. Mitteilung. Boromycin". Helv. Chim. Acta. 50 (6): 1533–1539. doi:10.1002/hlca.19670500612. PMID 6081908.
  • J. D. Dunitz; D. M. Hawley; D. Miklo; D. N. J. White; Yu. Berlin; R. Marui; V. Prelog (1971). "Structure of boromycin". Helv. Chim. Acta. 54 (6): 1709–1713. doi:10.1002/hlca.19710540624. PMID 5131791.
  1. ^ a b Kohno J, Kawahata T, Otake T, Morimoto M, Mori H, Ueba N, Nishio M, Kinumaki A, Komatsubara S, Kawashima K (June 1996). "Boromycin, an anti-HIV antibiotic". Biosci Biotechnol Biochem. 60 (6): 1036–7. doi:10.1271/bbb.60.1036. PMID 8695905.
  2. ^ Chien JY, Friedrich S, Heathman MA, de Alwis DP, Sinha V (October 2005). "Pharmacokinetics/Pharmacodynamics and the stages of drug development: role of modeling and simulation". AAPS J. 7 (3): E544–59. doi:10.1208/aapsj070355. PMC 2751257. PMID 16353932.
  3. ^ Mead S, Tagliavini F (2018). "Clinical trials". Human Prion Diseases. Handbook of Clinical Neurology. Vol. 153. pp. 431–444. doi:10.1016/B978-0-444-63945-5.00024-6. ISBN 9780444639455. PMID 29887150. {{cite book}}: |journal= ignored (help)
  4. ^ Mehta M, Schug B, Blume HH, Beuerle G, Jiang W, Koenig J, Paixao P, Tampal N, Tsang YC, Walstab J, Wedemeyer R, Welink J (November 2023). "The Global Bioequivalence Harmonisation Initiative (GBHI): Report of the fifth international EUFEPS/AAPS conference". Eur J Pharm Sci. 190: 106566. doi:10.1016/j.ejps.2023.106566. PMID 37591469. S2CID 260943533.
  5. ^ Lee J, Gong Y, Bhoopathy S, DiLiberti CE, Hooker AC, Rostami-Hodjegan A, Schmidt S, Suarez-Sharp S, Lukacova V, Fang L, Zhao L (November 2021). "Public Workshop Summary Report on Fiscal Year 2021 Generic Drug Regulatory Science Initiatives: Data Analysis and Model-Based Bioequivalence". Clin Pharmacol Ther. 110 (5): 1190–1195. doi:10.1002/cpt.2120. PMID 33236362. S2CID 227165142.
  6. ^ Pepin X, Dressman J, Parrott N, Delvadia P, Mitra A, Zhang X, Babiskin A, Kolhatkar V, Seo P, Taylor LS, Sjögren E, Butler JM, Kostewicz E, Tannergren C, Koziolek M, Kesisoglou F, Dallmann A, Zhao Y, Suarez-Sharp S (February 2021). "In Vitro Biopredictive Methods: A Workshop Summary Report". J Pharm Sci. 110 (2): 567–583. doi:10.1016/j.xphs.2020.09.021. PMID 32956678. S2CID 221842404. {{cite journal}}: Vancouver style error: initials in name 1 (help)
  7. ^ Kitaeva KV, Rutland CS, Rizvanov AA, Solovyeva VV (2020). "Cell Culture Based in vitro Test Systems for Anticancer Drug Screening". Front Bioeng Biotechnol. 8: 322. doi:10.3389/fbioe.2020.00322. PMC 7160228. PMID 32328489.
  8. ^ de Carvalho LP, Groeger-Otero S, Kreidenweiss A, Kremsner PG, Mordmüller B, Held J (2021). "Boromycin has Rapid-Onset Antibiotic Activity Against Asexual and Sexual Blood Stages of Plasmodium falciparum". Front Cell Infect Microbiol. 11: 802294. doi:10.3389/fcimb.2021.802294. PMC 8795978. PMID 35096650.
  9. ^ Kumar V, Bhargava G (2022). "Editorial: Protozoal infections: Treatment and challenges". Front Cell Infect Microbiol. 12: 1002602. doi:10.3389/fcimb.2022.1002602. PMC 9471550. PMID 36118046.
  10. ^ a b Abenoja J, Cotto-Rosario A, O'Connor R (March 2021). "Boromycin Has Potent Anti-Toxoplasma and Anti-Cryptosporidium Activity". Antimicrob Agents Chemother. 65 (4). doi:10.1128/AAC.01278-20. PMC 8097477. PMID 33468470.
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