Search Results (5)

Currently, cancer remains a global health problem. Despite the existence of several treatments, including chemotherapy, immunotherapy, and radiation therapy, the survival rate for most cancer patients, particularly those with metastasis, remains unsatisfactory. Thus, there is a continuous need to develop novel, effective therapies. In this work, 22 novel molecules containing selenium are reported, including seven Se-acylisoselenoureas synthesized from aliphatic carbodiimides as well as acylselenoureas with the same carbo- and heterocycles and aliphatic amines. After an initial screening at two doses (50 and 10 µM) in MDA-MB-231 (breast), HTB-54 (lung), DU-145 (prostate), and HCT-116 (colon) tumor cell lines, the ten most active compounds were identified. Additionally, these ten hits were also submitted to the DTP program of the NCI to study their cytotoxicity in a panel of 60 cancer cell lines. Compound 4 was identified as the most potent antiproliferative compound. The results obtained showed that compound 4 presented IC₅₀ values lower than 10 µM in the cancer cell lines, although it was not the most selective one. Furthermore, compound 4 was found to inhibit cell growth and cause cell death by inducing apoptosis partially via ROS production. Overall, our results suggest that compound 4 could be a potential chemotherapeutic drug for different types of cancer. Full article

Oxidative stress surrounding cancer cells provides them with certain growth and survival advantages necessary for disease progression. In this context, Se-containing molecules have gained attention due to their anticancer and antioxidant activity. In our previous work, we synthesized a library of 39 selenoesters containing functional groups commonly present in natural products (NP), which showed potent anticancer activity, but did not demonstrate high radical scavenger activity. Thus, 20 novel Se derivatives resembling NP have been synthesized presenting acylselenourea functionality in their structures. Radical scavenger activity was tested using DPPH assay and in vitro protective effects against ROS-induced cell death caused by H₂O₂. Additionally, antiproliferative activity was evaluated in prostate, colon, lung, and breast cancer cell lines, along with their ability to induce apoptosis. Compounds 1.I and 5.I showed potent cytotoxicity against the tested cancer cell lines, along with high selectivity indexes and induction of caspase-mediated apoptosis. These compounds exhibited potent and concentration-dependent radical scavenging activity achieving DPPH inhibition similar to ascorbic acid and trolox. To conclude, we have demonstrated that the introduction of Se in the form of acylselenourea into small molecules provides strong radical scavengers in vitro and antiproliferative activity, which may lead to the development of promising dual compounds. Full article

Selenium compounds are pivotal in medicinal chemistry for their antitumoral and antioxidant properties. Forty seven acylselenoureas have been designed and synthesized following a fragment-based approach. Different scaffolds, including carbo- and hetero-cycles, along with mono- and bi-cyclic moieties, have been linked to the selenium containing skeleton. The dose- and time-dependent radical scavenging activity for all of the compounds were assessed using the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays. Some of them showed a greater radical scavenging capacity at low doses and shorter times than ascorbic acid. Therefore, four compounds were evaluated to test their protective effects against H₂O₂-induced oxidative stress. One derivative protected cells against H₂O₂-induced damage, increasing cell survival by up to 3.6-fold. Additionally, in vitro cytotoxic activity of all compounds was screened against several cancer cells. Eight compounds were selected to determine their half maximal inhibitory concentration (IC₅₀) values towards breast and lung cancer cells, along with their selectivity indexes. The breast cancer cells turned out to be much more sensitive than the lung. Two compounds (5d and 10a) stood out with IC₅₀ values between 4.2 μM and 8.0 μM towards MCF-7 and T47D cells, with selectivity indexes greater than 22.9. In addition, compound 10b exhibited dual antioxidant and cytotoxic activities. Although further evidence is needed, the acylselenourea scaffold could be a feasible frame to develop new dual agents. Full article

Acid and base initiated cyclization and retrocyclization reactions of the selenoureas 1-6 and isoselenoureas 7-12 to fused 4H-1,3-selenazine and 1,2,3,4-tetrahydropyrimidine-4-one skeletons are reported. Fused 2-acylamino-4H-1,3-selenazine-4-ones 13-18 were formed by the action of concentrated sulfuric acid on acylselenoureas 1-6 or on 2,2-dimethylpropanoylisoselenoureas 10-12 at room temperature. On the other hand, benzoylisoselenoureas 7-9 were not obtained in this cyclocondensation under the same conditions. The reaction of potassium ethoxide on selenazines 13-18 in the ethanol solution evoked retrocyclization to the starting acylselenoureas 1-6. Both types of the title compounds, i.e. selenoureas 1-6 and isoselenoureas 7-12, were deprotonated in a methanol solution of potassium hydroxide used in an equimolar amount, giving rise to potassium salts 19-24, which were isolated only for the thiophene series. By heating the separated potassium salts 20, 21, 23 and 24 in the methanol solution provided, deacylation and isoselenoureas 26, 27 were formed. The in situ prepared salts 19, 22 cyclized under the same conditions with deacylation to 4-selanyl-3,4-dihydroquinazoline-4-one 28. The title compounds 1-6, 7-12 and products of their deacylation 26, 27 on boiling in methanolic potassium hydroxide cyclized to the corresponding fused 2-selenoxo-1,2,3,4-tetrahydropyrimidine-4-one potassium salts. These compounds provided pyrimidine-4-ones 28-30 on acidification. Acid initiated retrocyclization 28-30 to the corresponding 2-amino-4H-1,3-selenazine-4-ones was unsuccessful. C, H, N, Se elemental analyses, FTIR, 1H-NMR, and 13C-NMR spectroscopies supported the structure of synthesized compounds.A short review on cardiotonic steroids and their analogues is presented. The natural, semisynthetic and synthetic derivatives, as well as their mechanism of action and structure-activity relationships are shown, with a special reference to aminoguanidine derivatives. Full article

Synthesis, isomerisation and structure elucidation of the title compounds 1–6 and its isomers 7–12 by FTIR, ¹H, ¹³C, ¹⁵N, ⁷⁷Se NMR spectroscopy is reported. Ethyl 2–(3–acylselenoureido)thiophene–3–carboxylates and their benzoanalogues (where acyl is benzoyl and pivaloyl) were prepared by addition of ethyl 2–aminothiophene–3–carboxylates and ethyl 2–aminobenzoate on benzoyl– or pivaloylisoselenocyanate in acetone solution. An isomerization of 1–6 to the corresponding 3–acylisoselenoureas 7–12 was obtained. The isomerisation proceeds either by irradiation with light (340–400 nm) or in the case of benzoylderivatives 1, 3, 5 by treatment with acetic acid. On the other hand the acid action in the pivaloyl set inhibited this isomerisation and evoked the retroisomerisation reaction of 8, 10, 12 to 2, 4, 6. Thermal analyses showed that isomerisation can be initiated also by heating. These changes proceed in the solid phase as an exothermic process at an elevated temperature but always below the temperature of melting. The structure 2 was supported by X–ray analysis. Molecular design of 2 and 8 was modeled during application of ab initio quantum chemistry calculation. Full article