Synthesis and Biological Evaluation of N6-Cycloalkyl Derivatives of 1-Deazaadenine Nucleosides: A New Class of Anti-Human Immunodeficiency Virus Agents

A series of 5′- Oacyl derivatives of thymidine (dThd) were prepared by direct acylation of thymidine using the Mitsunobu reaction. Further reaction of the bromo analogues with sodium azide gave azido ester analogues. Anti-human immunodeficiency virus type 1 (HIV-1) activities were determined against HIV-infected T4 lymphocytes. 5′- O-(12-Azidododecanoyl)thymidine exhibited moderate activity (EC50 4.6 μM) against HIV-infected T4 lymphocytes. 5- O-(2-Bromotetradecanoyl)-thymidine was found to be the most stable ester (t1/2 15.3 min) to hydrolysis by porcine liver esterase in vitro. Partition coefficients (P) in n-octanol-phosphate buffer were determined (log10 P range 4.15–6.72) and compared with the theoretical values calculated (log10 P 3.96–6.53) using the PALLAS program. Anti-HIV structure-activity data suggest that the experimental partition coefficient should be in the log10 P 4.6–4.8 range for optimum anti-HIV activity. The structures of these thymidine analogues were optimized using molecular mechanics (MM+ force field) and semi-empirical quantum mechanics PM3 calculations. The moderately active compounds adopted a similar C-2′ endo sugar conformation and exhibited similar energies for the lowest energy conformer. A quantitative structure-activity relationship (QSAR) regression equation was developed, based on the optimized structures and anti-HIV data using the SciQSAR program, which showed that log P was a determinant of anti-HIV activity.

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Design, Synthesis, and Biological Evaluation of Novel Hybrid Dicaffeoyltartaric/Diketo Acid and Tetrazole-Substitutedl-Chicoric Acid Analogue Inhibitors of Human Immunodeficiency Virus Type 1 Integrase

Journal of Medicinal Chemistry ◽

10.1021/jm1010594 ◽

2010 ◽

Vol 53 (22) ◽

pp. 8161-8175 ◽

Cited By ~ 33

Author(s):

David C. Crosby ◽

Xiangyang Lei ◽

Charles G. Gibbs ◽

Brenda R. McDougall ◽

W. Edward Robinson ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Biological Evaluation ◽

Design Synthesis ◽

Chicoric Acid ◽

Acid Analogue ◽

Immunodeficiency Virus ◽

Synthesis And Biological Evaluation

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Synthesis and Biological Evaluation of Novel Isopropanolamine Derivatives as Non-peptide Human Immunodeficiency Virus Protease Inhibitors

Chemical and Pharmaceutical Bulletin ◽

10.1248/cpb.56.1147 ◽

2008 ◽

Vol 56 (8) ◽

pp. 1147-1152 ◽

Cited By ~ 4

Author(s):

Lijun Zhou ◽

Qingang Yang ◽

Yong Wang ◽

Youhong Hu ◽

Xiaomin Luo ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Protease Inhibitors ◽

Biological Evaluation ◽

Human Immunodeficiency Virus Protease ◽

Immunodeficiency Virus ◽

Synthesis And Biological Evaluation

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Pyrazol(in)e derivatives of curcumin analogs as a new class of anti-Trypanosoma cruzi agents

Future Medicinal Chemistry ◽

10.4155/fmc-2020-0349 ◽

2021 ◽

Author(s):

Dimitris Matiadis ◽

Tatiana Saporiti ◽

Elena Aguilera ◽

Xavier Robert ◽

Christophe Guillon ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Mammalian Cells ◽

Triosephosphate Isomerase ◽

Biological Evaluation ◽

Significant Activity ◽

New Class ◽

New Family ◽

Curcumin Analogs ◽

Synthesis And Biological Evaluation ◽

Derivatives Of

Aim: We report the synthesis and biological evaluation of a small library of 15 functionalized 3-styryl-2-pyrazolines and pyrazoles, derived from curcuminoids, as trypanosomicidal agents. Methods & results: The compounds were prepared via a cyclization reaction between the corresponding curcuminoids and the appropriate hydrazines. All of the derivatives synthesized were investigated for their trypanosomicidal activities. Compounds 4a and 4e showed significant activity against epimastigotes of Trypanosoma cruzi, with IC50 values of 5.0 and 4.2 μM, respectively, accompanied by no toxicity to noncancerous mammalian cells. Compound 6b was found to effectively inhibit T. cruzi triosephosphate isomerase. Conclusion: The up to 16-fold higher potency of these derivatives compared with their curcuminoid precursors makes them a promising new family of T. cruzi inhibitors.

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