Oxythiamine (OT) and 3-deazathiamine (DAT) are the antimetabolites of thiamine. The aim of study was to compare the effects of OT and DAT pyrophosphates (-PP) on the kinetics of mammalian pyruvate dehydrogenase complex (PDHC) and the in vitro culture of HeLa cells. The kinetic study showed that 3-deazathiamine pyrophosphate (DATPP) was a much stronger competitive inhibitor (K_i = 0.0026 μM) of PDHC than OTPP (K_i = 0.025 μM). Both K_i values were much lower versus K _m for thiamine pyrophosphate (0.06 μM). However, DATPP added to the culture medium for the HeLa cells culture did not hamper the rate of cell growth and showed not significant impact on the viability of the cells, whereas OTPP and OT showed a significant cytostatic effect. The differences between the thiamine antivitamins in their effect on cell growth in vitro may be due to differences in physicochemical properties and difficulty in DAT transport across the cell membrane.

Magnetite and gallium substituted cuboferrites with a composition of Ga_xFe_3−xO₄ (0 ≤ x ≤ 1.4) were fabricated by thermal decomposition from acetylacetonate salts. The effect of Ga³⁺ cation substitution on the structural and thermomagnetic behavior of 4–12 nm sized core-shell particles was explored by X-ray and neutron diffraction, small angle neutron scattering, transmission electron microscopy, Mössbauer spectroscopy, and calorimetric measurements. Superparamagnetic (SPM) behavior and thermal capacity against increasing gallium concentration in nanoferrites were revealed. The highest heat capacity typical for Fe₃O₄@Ga_0.6Fe_2.4O₄ and Ga_0.6Fe_2.4O₄@Fe₃O₄ is accompanied by a slight stimulation of fibroblast culture growth and inhibition of HeLa cell growth. The observed effect is concentration dependent in the range of 0.01–0.1 mg/mL and particles of Ga_0.6Fe_2.4O₄@Fe₃O₄ design have a greater effect on cells. Observed magnetic heat properties, as well as interactions with tumor and healthy cells, provide a basis for further biomedical research to use the proposed nanoparticle systems in cancer thermotherapy (magnetic hyperthermia).

It is important to search for cytostatic compounds in order to fight cancer. One of them could be 2′-methylthiamine, which is a thiamine antimetabolite with an additional methyl group at the C-2 carbon of thiazole. So far, the cytostatic potential of 2′-methylthiamine has not been studied. We have come forward with a simplified method of synthesis using commercially available substrates and presented a comparison of its effects, as boosted by oxythiamine, on normal skin fibroblasts and HeLa cancer cells, having adopted in vitro culture techniques. Oxythiamine has been found to inhibit the growth and metabolism of cancer cells significantly better than 2′-methylthiamine (GI₅₀ 36 and 107 µM, respectively), while 2′-methylthiamine is more selective for cancer cells than oxythiamine (SI = 180 and 153, respectively). Docking analyses have revealed that 2′-methylthiamine (ΔG −8.2 kcal/mol) demonstrates a better affinity with thiamine pyrophosphokinase than thiamine (ΔG −7.5 kcal/mol ) and oxythiamine (ΔG −7.0 kcal/mol), which includes 2′-methylthiamine as a potential cytostatic. Our results suggest that the limited effect of 2′-methylthiamine on HeLa arises from the related arduous transport as compared to oxythiamine. Given that 2′-methylthiamine may possibly inhibit thiamine pyrophosphokinase, it could once again be considered a potential cytostatic. Thus, research should be carried out in order to find the best way to improve the transport of 2′-methylthiamine into cells, which may trigger its cytostatic properties.

Cytostatic and pro-apoptotic effects of selenium steroid derivatives against HeLa cells were determined. The highest cytostatic activity was shown by derivative 4 (GI₅₀ 25.0 µM, almost complete growth inhibition after three days of culture, and over 97% of apoptotic and dead cells at 200 µM). The results of our study (cell number measurements, apoptosis profile, relative expression of apoptosis-related APAF1, BID, and mevalonate pathway-involved HMGCR, SQLE, CYP51A1, and PDHB genes, and computational chemistry data) support the hypothesis that tested selenosteroids induce the extrinsic pathway of apoptosis by affecting the cell membrane as cholesterol antimetabolites. An additional mechanism of action is possible through a direct action of derivative 4 to inhibit PDHB expression in a way similar to steroid hormones.