Journal
BIOORGANIC CHEMISTRY
Volume 125, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2022.105924
Keywords
Triterpenes; Semisynthetic triterpenes; Cytotoxicity; Anti-inflammation; Pyrazines
Funding
- Universidad Nacional Autonoma de Mexico (Direccion General de Asuntos del Personal Academico) [PAPIIT IG200821]
- Programa de Maestria y Doctorado en Ciencias Quimicas (UNAM)
- Consejo Nacional de Ciencia y Tecnologia [307784]
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The semisynthesis of novel derivatives of lupeol palmitate and 3 beta-palmitoyloxy-olean-12-ene was conducted, and their cytotoxic and anti-inflammatory activities were evaluated. Several derivatives showed significant inhibition of tumor cell lines, and the modification of compound structure affected their anti-inflammatory activity. Further investigation revealed that compounds 7, 10, and 11 may exert their effects by binding to the NF-kappa B receptor, and these compounds have potential for further research.
The semisynthesis of novel derivatives of lupeyl palmitate and 3 beta-palmitoyloxy-olean-12-ene by introduction of a pyrazine at C-2 / C-3 and modifications of the relatively unexplored C-30 position of lupeol derivatives was conducted, and their cytotoxic and anti-inflammatory activities were evaluated. The derivatives 7, 10 and 11 significantly inhibited the tumor cell lines U251, K562, HCT-15, MCF-7 and SKLU-1, and compounds 7 and 11 were more active (IC50 25.4 +/- 2.0 mu M and 7.1 +/- 0.4 mu M, respectively) than the positive control (etoposide (IC50 31.5 +/- 2.2 mu M) in the tumor line PC-3. Introduction of the pyrazine at C-2 / C-3 in compounds 1 and 2 or modification at C-30 of compound 1 decreased the anti-inflammatory activity in the TPA-induced mouse ear edema. Following the results of the PASS online evaluation of the potential biological activity of the natural compounds and their derivatives, the inhibition of pNF-kappa B translocation to the prostate cancer (PC-3) cell nucleus was investigated and the binding mode of compounds 7, 10 and 11 with the human NF-kappa B receptor was explored by a molecular docking study. These derivatives bound directly or close to the amino acids that form the DNA recognition site. The ADMET physicochemical parameters of the fifteen compounds were further analyzed in silica using Molinspiration calculations indicating the potential of compounds 7, 10 and 11 for further investigation.
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