In Search of Effective Anticancer Agents-Novel Sugar Esters Based on Polyhydroxyalkanoate Monomers.

Wojciech Snoch,Andrzej J Bojarski,Ewelina Jarek,Francisco J Plou,Maciej Guzik,Jakub Staroń,Tomasz Witko,Dawid Wnuk

doi:10.3390/ijms22137238

Abstract

Cancer is one of the deadliest illness globally. Searching for new solutions in cancer treatments is essential because commonly used mixed, targeted and personalized therapies are sometimes not sufficient or are too expensive for common patients. Sugar fatty acid esters (SFAEs) are already well-known as promising candidates for an alternative medical tool. The manuscript brings the reader closer to methods of obtaining various SFAEs using combined biological, chemical and enzymatic methods. It presents how modification of SFAE’s hydrophobic chains can influence their cytotoxicity against human skin melanoma and prostate cancer cell lines. The compound’s cytotoxicity was determined by an MTT assay, which followed an assessment of SFAEs’ potential metastatic properties in concentrations below IC50 values. Despite relatively high IC50 values (63.3–1737.6 μM) of the newly synthesized SFAE, they can compete with other sugar esters already described in the literature. The chosen bioactives caused low polymerization of microtubules and the depolymerization of actin filaments in nontoxic levels, which suggest an apoptotic rather than metastatic process. Altogether, cancer cells showed no propensity for metastasis after treating them with SFAE. They confirmed that lactose-based compounds seem the most promising surfactants among tested sugar esters. This manuscript creates a benchmark for creation of novel anticancer agents based on 3-hydroxylated fatty acids of bacterial origin.

Highlights

Introduction iationsAccording to statistics provided by the World Human Organization, cancer is one of the deadliest illness globally
We present the description on biocatalytic synthesis of novel Sugar fatty acid esters (SFAEs) and their structural characterization by infrared and NMR spectroscopies combined with mass spectrometry analysis
Samples were submitted to 1 H and 19 F NMR analyses, which confirmed the structural modification of the PHN (R)-3-hydroxyacids and the synthesis of the (R)-3-(2,2,2-trifluoroethoxy) nonanoic a (R)-3-(2,2,2-trifluoroethoxy)heptanoic acids

Summary

Introduction

Introduction iationsAccording to statistics provided by the World Human Organization, cancer is one of the deadliest illness globally. Prostate, colorectal, stomach and liver cancers are the most common types of cancer in men, while breast, colorectal, lung, cervical and thyroid cancers are the most common among women [1]. Statistics, 2019’, the most prevalent cancers in 2019 in the USA were prostate (3,650,030), colon and rectum (776,120), skin melanoma (684,470) among males and breast (3,861,520), uterine corpus (807,860), and colon and rectum (768,650) among females [2]. Prostate cancer was the fifth most common cancer in Europe in 2018 (450,000) [3]. These statistics bring us to conclusions that searching for new solutions in melanoma and prostate cancer treatment is still essential

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