Anti-AIDS agents. Part 58: Synthesis and anti-HIV activity of 1-thia-di-O-(−)-camphanoyl-(+)-cis-khellactone (1-thia-DCK) analogues

Xia, Peng; Yin, Zhenhua; Chen, Ying; Zhang, Qian; Zhang, Beina; Yi, Xin; Yang, Zheng; Kilgore, Nicole; Wild, Carl; Morris‐Natschke, Susan L.; Lee, Kuo Hsiung̀

doi:10.1016/j.bmcl.2004.03.051

Cited by 9 publications

(6 citation statements)

References 7 publications

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“…In addition, previous bioisosteric replacement study demonstrated that 1-thia, 1′-thia, and 1-aza DCKs maintained potent antiviral activity or had better activity against HIV compared with 2 4,5,7. These results motivated us to synthesize compounds 13 – 16 with sulfur or nitrogen rather than oxygen linked to the camphanoyl group of the seco-DCKs…”

Section: Resultsmentioning

confidence: 99%

Anti-AIDS agents 82: Synthesis of seco-(3′R,4′R)-3′,4′-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives as novel anti-HIV agents

Tang

Qian

Zhang

et al. 2010

Bioorganic & Medicinal Chemistry

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Thirteen novel seco-DCK analogs (4–16) with several new skeletons were designed, synthesized and screened for in vitro anti-HIV-1 activity. Among them, three compounds (5, 13, and 16) showed moderate activity, and compound 9 exhibited the best activity with an EC50 value of 0.058 μM and a therapeutic index (TI) of 1000. The activity of 9 was better than that of 4-methyl DCK (2, EC50: 0.126 μM, TI: 301.2) in the same assay. Additionally, 9 also showed antiviral activity against a multi-RT inhibitor-resistant strain (RTMDR), which is insensitive to most DCK analogs. Compared with 2, compound 9 has a less complex structure, fewer hydrogen-bond acceptors, and a reduced log P value. Therefore, it is likely to exhibit better ADME, and appears to be a promising new lead for further development as an anti-HIV candidate.

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Section: Resultsmentioning

confidence: 99%

Anti-AIDS agents 82: Synthesis of seco-(3′R,4′R)-3′,4′-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives as novel anti-HIV agents

Tang

Qian

Zhang

et al. 2010

Bioorganic & Medicinal Chemistry

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“…In SAR studies, replacing an oxygen atom in the lactone ring of 146 with sulfur or nitrogen led to analogs with significant potency, with EC 50 values in the lower micromolar to nanomolar range 112-114. For example, replacing the carbonyl oxygen of 4-methyl-DCK with sulfur (-OC=S) giving 158 (4-MeDCK thiolactone) led to no loss or improvement in potency when assayed in CEM-SS cells (Figure 31).…”

Section: Suksdorfin Derivativesmentioning

confidence: 99%

“…For example, replacing the carbonyl oxygen of 4-methyl-DCK with sulfur (-OC=S) giving 158 (4-MeDCK thiolactone) led to no loss or improvement in potency when assayed in CEM-SS cells (Figure 31). 112 Similarly, replacing the alcoholic oxygen of the lactone with nitrogen (-NHC=O, 159 )113 or sulfur (-SC=O, 160 )114 led to equipotent or slightly more potent compounds, compared with 146 (-OC=O).…”

Section: Suksdorfin Derivativesmentioning

confidence: 99%

Discovery and Development of Natural Product-Derived Chemotherapeutic Agents Based on a Medicinal Chemistry Approach

2010

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Medicinal plants have long been an excellent source of pharmaceutical agents. Accordingly, the long term objectives of the author's research program are to discover and design new chemotherapeutic agents based on plant-derived compound leads by using a medicinal chemistry approach, which is a combination of chemistry and biology. Different examples of promising bioactive natural products and their synthetic analogs, including sesquiterpene lactones, quassinoids, naphthoquinones, phenylquinolones, dithiophenediones, neo-tanshinlactone, tylophorine, suksdorfin, DCK, and DCP, will be presented with respect to their discovery and preclinical development as potential clinical trial candidates. Research approaches include bioactivity- or mechanism of action-directed isolation and characterization of active compounds, rational drug design-based modification and analog synthesis, as well as structure-activity relationship and mechanism of action studies. Current clinical trials agents discovered by the Natural Products Research Laboratories, University of North Carolina, include bevirimat (dimethyl succinyl betulinic acid), which is now in Phase IIb trials for treating AIDS. Bevirimat is also the first in a new class of HIV drug candidates called “maturation inhibitors”. In addition, an etoposide analog, GL-331, progressed to anticancer Phase II clinical trials, and the curcumin analog JC-9 is in Phase II clinical trials for treating acne and in development for trials against prostate cancer. The discovery and development of these clinical trials candidates will also be discussed.

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“…Also, these thiazole containing drugs are used as antitumor antimalarial , antimicrobial , anti‐inflammatory and anti‐hypolipidemic agents. On the other hand, the S‐ligation molecules and pharmaceuticals such as thiochromanes are reported to exhibit anti‐inflammatory, anti‐bacterial, anti‐psychiatric, anti‐hyperplasia, anti‐cancer, and analgesic activities . In view of all these findings, it seems of considerable interest to synthesize new thiazole derivatives with thiochromane moiety.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antimicrobial Activity and Molecular Docking Study of Thiazole Derivatives

Farghaly

Abdallah

Khedr

et al. 2017

Journal of Heterocyclic Chem

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in Wiley Online Library (wileyonlinelibrary.com).The reaction of 4-thiochromane thiocarbohydrazone with a series of hydrazonoyl halides in dioxane in the presence of triethylamine afforded novel thiochromane derivatives incorporating 1,3-thiazole moiety. The structure of the latter compounds was established by elemental analysis and spectral technique and by their chemical transformation. Moreover, the antimicrobial activity of the newly synthesized compounds was screened and the results showed that some compounds have higher activity than the applied fungicide and bactericide. The antimicrobial activity of the most active compounds was interpreted by molecular docking study.

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Anti-AIDS agents. Part 58: Synthesis and anti-HIV activity of 1-thia-di-O-(−)-camphanoyl-(+)-cis-khellactone (1-thia-DCK) analogues

Cited by 9 publications

References 7 publications

Anti-AIDS agents 82: Synthesis of seco-(3′R,4′R)-3′,4′-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives as novel anti-HIV agents

Anti-AIDS agents 82: Synthesis of seco-(3′R,4′R)-3′,4′-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives as novel anti-HIV agents

Discovery and Development of Natural Product-Derived Chemotherapeutic Agents Based on a Medicinal Chemistry Approach

Synthesis, Antimicrobial Activity and Molecular Docking Study of Thiazole Derivatives

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