Cited by 123Marine Sponges and Natural ProductsSynthesis and Biological ActivityMicrobial Natural Products and Biosynthesis

New manzamine alkaloids from an Indo-Pacific sponge. Pharmacokinetics, oral availability, and the significant activity of several manzamines against HIV-I, AIDS opportunistic infections, and inflammatory diseases

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Yousaf, Muhammad, Hammond, Nicholas L., Peng, Jiangnan, Wahyuono, Subagus, McIntosh, Kylie A., Charman, William N., Mayer, Alejandro M. S., Hamann, Mark T.·2004·Journal of Medicinal Chemistry

Abstract

12,28-Oxamanzamine A (1), 12,28-oxa-8-hydroxymanzamine A (2), and 31-keto-12,34-oxa-32,33-dihydroircinal A (3) were isolated from two collections of an Indo-Pacific sponge, and their structures were assigned on the basis of 1D and 2D NMR spectroscopic data. These compounds possess a novel manzamine-type ring system generated through a new ether bridge formed between carbons 12 and 28 or between carbons 12 and 34 of the typical manzamine structure and add to our growing understanding of manzamine SAR and metabolism. Based on molecular modeling studies, the formation of these oxidation products is highly sterically favored. The potent antiinflammatory, antifungal, and anti-HIV-1 activity for a number of previously reported manzamines is also presented in addition to the pharmacokinetic studies of manzamine A (5). Oral and intravenous pharmacokinetic studies of manzamine A in rats indicated the compound to have low metabolic clearance, a reasonably long pharmacokinetic half-life, and good absolute oral bioavailability of 20.6%, which supports the value of these compounds as potential leads for further preclinical assessment and possible development.

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Authors
Yousaf, M., Hammond, N. L., Peng, J., Wahyuono, S., McIntosh, K. A., Charman, W. N., Mayer, A. M. S., & Hamann, M. T.
Affiliations
Universitas Gadjah Mada (ID)
Corresponding author
Hamann, Mark T.
Venue
Journal of Medicinal Chemistry
Published
2004-05-27
Volume
47
Issue
14
Pages
3512-3517
ISSN
  • 0022-2623 (ISSN-L)
  • 1520-4804
OpenAlex
W2023736261
Cited by
119
References
15
Citations by year
2026: 2 · 2025: 7 · 2024: 5 · 2023: 7 · 2022: 8 · 2021: 2 · 2020: 11 · 2019: 7 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 5
FWCI
4.93
Type
journal article
Language
en
Open access
Locations
  • Journal of Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R01AI036596)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Marine Sponges and Natural Products
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Synthesis and Biological Activity
  • Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
Keywords
manzamine alkaloids, manzamine A, sponge natural products, structure-activity relationship, pharmacokinetics, oral bioavailability, anti-HIV-1 activity, antifungal activity, anti-inflammatory activity, marine natural products
MeSH terms
Administration, Oral, Animals, Anti-Inflammatory Agents, Anti-Bacterial Agents, Antifungal Agents, Biological Availability, Carbazoles, Carbolines, Fourier Analysis, Indoles, Injections, Intravenous, Male, Microbial Sensitivity Tests, Models, Molecular, Molecular Conformation, Magnetic Resonance Spectroscopy, Porifera, Pyrroles, Quinolines, Mass Spectrometry, Structure-Activity Relationship, HIV-1, AIDS-Related Opportunistic Infections, Rats, Sprague-Dawley, Anti-HIV Agents, Rats

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