Design and Synthesis of Mycophenolic Acid Analogues for Osteosarcoma Cancer Treatment

IF 3.8 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY ACS Bio & Med Chem Au Pub Date : 2024-10-17 DOI:10.1021/acsbiomedchemau.4c0007910.1021/acsbiomedchemau.4c00079

Patamawadee Silalai, Pimpisa Teeyakasem, Dumnoensun Pruksakorn* and Rungnapha Saeeng*,

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Abstract

Mycophenolic acid (MPA), a natural compound, was modified to new MPA analogues via the classical method of silylation and esterification. Their cytotoxicity was evaluated in vitro on four osteosarcoma cancer cell lines (MNNG/HOS, U2OS, 143B, and SaOS-2) and human normal cells (hFOB 1.19). The most potent silicon-containing compound 2d (R¹ = TPS, R² = H) exhibited good cytotoxic activity against all osteosarcoma cancer cell lines with IC₅₀ values ranging from 0.64 to 2.27 μM and showing low cytotoxicity against normal cells. Further investigations revealed that compound 2d (R¹ = TPS, R² = H) displayed significant inhibition of IMPDH2 with K_i_app 1.8 μM. Furthermore, molecular modeling studies were performed to investigate the binding affinity of 2d (R¹ = TPS, R² = H) which can effectively bind to critical amino acids of three proteins (vascular endothelial growth factor receptor 2; VEGFR-2, cyclin-dependent kinase 2; CDK2, inosine-5′-monophosphate dehydrogenase; IMPDH) involved in cancer therapy. This finding suggests that triphenylsilyl-MPA (TPS-MPA) analogue could serve as a promising starting point for developing new anticancer drugs for osteosarcoma.

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ACS Bio & Med Chem Au 药物、生物、化学-

CiteScore

4.10

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0.00%

发文量

期刊介绍： ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.