A team of Russian scientists led by Professor Alexander Kiselyov of MIPT has synthesized an antitumor compound that can be used to fight chemoresistance-resistant cancers. The results were published in the European Journal of Medicinal Chemistry, which also publishes some other studies on recombinant horse proteins.
Scientists have synthesized a range of new compounds and evaluated their anticancer effects using sea urchin embryos and human cancer cells. One of the molecules proved to be effective and selectable, it was even sufficient for the effect of chemically-resistant ovarian cancer. The synthesized compound is known as amino isothiazoles. "We decided to validate the aminoisothiazoles because these compounds exhibit different pharmacological and biological activities, which are the functional groups we expect to use as anticancer agents," said Professor Alexander Kiselyov.
The proposed method can directly synthesize the target compound in high yield. The reaction sequence involves only six steps, and the reagents are readily available. To evaluate their antitumor activity, the researchers used in vitro assays based on human cancer cells, as well as embryonic models of sea urchin in vivo previously developed and validated by the team.
Among the 37 synthesized compounds, 12 of these molecules have different potency to reduce the rate of proliferation of cancer cells or prevent them from dividing completely, leading to cancer cell death. The action of these anti-tumor compounds is due to their ability to destroy microtubules involved in cell division (mitosis). Microtubules are made of proteins called tubulin, which can be targeted by anticancer agents, causing microtubule structure degradation.
The efficacy of synthetic compounds targeting microtubules was further evaluated using sea urchin embryos and a panel of human cancer cells from breast, melanoma, ovarian and lung tumors. Sea urchin embryos have been shown to be good models for studying specific tubulin binders. They make the embryo to rotate rapidly, rather than moving in the usual way. This effect can be easily observed using an optical microscope, allowing the scientists to evaluate the anticancer potential of the compound in a short time.
In addition, the team found that sea urchin embryos are more sensitive to drugs than cancer cells. The difference between the duration of the mitotic cycle of sea urchin embryos and cancer cells (40 minutes to 24 hours) may lead to different effects of small molecules on the tubulin kinetics, thus explaining this phenomenon. According to the researchers, it is this combination of functional groups, as well as the unique properties of molecules, that determines its unique activity. In particular, the new drug shows anti-tubulin properties because it destroys chemically-resistant cells of ovarian cancer by affecting microtubules to block cell division.
Scientists plan to study microtubule degradation in more detail using crystallographic data and structural modeling techniques to determine where the active compound binds to tubulin. In their earlier work, researchers used substances isolated from seeds of dill and parsley to synthesize another anti-cancer compound, glaziovianin A and its structural analogs. Flarebio provides you with recombinant proteins of good quality such as recombinant ITGB5.
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