Topic
Calanolides
About: Calanolides is a research topic. Over the lifetime, 39 publications have been published within this topic receiving 1349 citations.
Papers
TL;DR: Calanolide A was active not only against the AZT-resistant G-9106 strain of HIV-1 but also against the pyridinone-resistant A17 strain, which was of particular interest since the A17 virus is highly resistant to previously known HIV- 1 specific, non-nucleoside RT inhibitors.
Abstract: Eight new coumarin compounds (1-8) were isolated by anti-HIV bioassay-guided fractionation of an extract of Calophyllum lanigerum. The structures of calanolide A (1), 12-acetoxycalanolide A (2), 12-methoxycalanolide A (3), calanolide B (4), 12-methoxycalanolide B (5), calanolide C (6) and related derivatives 7 and 8 were solved by extensive spectroscopic analyses, particularly HMQC, HMBC, and difference NOE NMR experiments. The absolute stereochemistry of calanolide A (1) and calanolide B (4) was established by a modified Mosher's method. Calanolides A (1) and B (4) were completely protective against HIV-1 replication and cytopathicity (EC50 values of 0.1 microM and 0.4 microM, respectively), but were inactive against HIV-2. Some of the related compounds also showed evidence of anti-HIV-1 activity. Studies with purified bacterial recombinant reverse transcriptases (RT) revealed that the calanolides are HIV-1 specific RT inhibitors. Moreover, calanolide A was active not only against the AZT-resistant G-9106 strain of HIV-1 but also against the pyridinone-resistant A17 strain. This was of particular interest since the A17 virus is highly resistant to previously known HIV-1 specific, non-nucleoside RT inhibitors (e.g., TIBO; BI-RG-587; L693,593) which comprise a structurally diverse but apparently common pharmacologic class. The calanolides represent a substantial departure from the known class and therefore provide a novel new anti-HIV chemotype for drug development.
593 citations
TL;DR: The hexane, acetone and methanol extracts of Calophyllum brasiliense leaves were fractionated following a three bioassay guide and led to the isolation of three anti HIV-1 dipyranocoumarins: calanolides A and B and soulattrolide.
Abstract: The hexane, acetone and methanol extracts of Calophyllum brasiliense leaves were fractionated following a three bioassay guide: high HIV-1 RT inhibition, low cytotoxicity on MT2 cells and high inhibition of HIV-1 IIIb/LAV replication. This led to the isolation of three anti HIV-1 dipyranocoumarins: calanolides A and B and soulattrolide. In contrast, other isolated compounds such as apetalic acid, isoapetalic acid, a structural isomer of isoapetalic acid, friedelin, canophyllol and amentoflavone were devoid of HIV-1 RT inhibitory activity. Calanolide C was also obtained as a natural product and showed moderate inhibitory properties.
95 citations
TL;DR: The inhibitory effects of these coumarins on Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells are discussed.
Abstract: Continuing our search for cancer chemopreventive agents from natural sources, we examined constituents of the stem bark of Calophyllum brasiliense. Three new 4-substituted coumarins named brasimarins A (2), B (3), and C (4) were isolated and characterized, along with 11 known coumarins belonging to the calanolides or inophyllums. We also discuss the inhibitory effects of these coumarins on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells.
93 citations
TL;DR: Strong, selective mycobactericidal activity of these calanolides will be useful in identifying pathways for killing both R- and NR-Mtb, as well as in further structure-based design of more effective and drug-like antimycobacterial agents.
Abstract: It is urgent to introduce new drugs for tuberculosis to shorten the prolonged course of treatment and control drug-resistant Mycobacterium tuberculosis (Mtb) One strategy toward this goal is to develop antibiotics that eradicate both replicating (R) and nonreplicating (NR) Mtb Naturally occurring (+)-calanolide A was active against R-Mtb The present report details the design, synthesis, antimycobacterial activities, and structure–activity relationships of synthetic calanolides We identified potent dual-active nitro-containing calanolides with minimal in vitro toxicity that were cidal to axenic Mtb and Mtb in human macrophages, while sparing Gram-positive and -negative bacteria and yeast Two of the nitrobenzofuran-containing lead compounds were found to be genotoxic to mammalian cells Although genotoxicity precluded clinical progression, the profound, selective mycobactericidal activity of these calanolides will be useful in identifying pathways for killing both R- and NR-Mtb, as well as in further s
73 citations
TL;DR: In this paper, the synthetic routes leading to the synthesis of the natural 4-phenyl, 4-propyl and 4-methyl coumarins isolated from Calophyllum sp are presented.
Abstract: Synthetic routes leading to the synthesis of the natural 4-phenyl, 4-propyl and 4-methyl coumarins isolated from Calophyllum sp. are presented. 4-Aryl or -alkyl, 8- and 6-acyl 5,7-dihydroxy coumarins were chromenylated and then methylated at the 5 or 7 positions. A 4-step hydrobromination–bromination–double dehydrobromination sequence converted the 2-methylbutanoyl side chain into the (E)-2-methylbut-2-enoyl (tigloyl) group to give calophyllolide, oblongulide, their natural 4-propyl analogue and the corresponding regioisomers. Demethylation and cyclisation of the tigloyl group gave inophyllums C and E, tomentolides A and B, and calanolide D. Sodium boranuide reduction of the 2,3-dimethylchromanone ring afforded inophyllums A, B, D and P, soulattrolide, calanolides A-C, costatolide, and cordatolides A and B. The structures of calanolides C and D, oblongulide and apetatolide have been reassigned. The previously unknown stereochemistry about the 2,3-dimethylchromanone ring of tomentolides A and B has been established as trans.
49 citations
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| 2021 | 1 |
| 2020 | 1 |
| 2016 | 2 |
| 2015 | 2 |
| 2014 | 3 |
| 2013 | 1 |