Background: Several drugs with inotropic activity have been synthesized; however, there is very little information on biological activity exerted by steroid derivatives in the cardiovascular system. Objective: The aim of this research was to prepare a steroid-pyridine derivative to evaluate the effect it exerts on left ventricular pressure and characterize its molecular interaction. Methods: The first stage was carried out through the synthesis of a steroid-pyridine derivative using some chemical strategies. The second stage involved the evaluation of the biological activity of the steroid-pyridine derivative on left ventricular pressure using a model of heart failure in the absence or presence of the drugs, such as flutamide, tamoxifen, prazosin, metoprolol, indomethacin, and nifedipine. Results: The results showed that steroid-pyridine derivative increased left ventricular pressure in a dose-dependent manner (0.001-100 nM); however, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These results indicate that positive inotropic activity produced by the steroid-pyridine derivative was via calcium channel activation. Furthermore, the biological activity exerted by the steroid-pyridine derivative on the left ventricle produces changes in cAMP concentration. Conclusion: It is noteworthy that positive inotropic activity produced by this steroid-pyridine derivative involves a different molecular mechanism compared to other positive inotropic drugs. Therefore, this steroid could be a good candidate for the treatment of heart failure.
Prostate cancer is one of the leading causes of death among men worldwide; Some data suggest that ribosomal S6 p90 kinase (RSK 1-4), which belongs to the group of highly conserved Ser/Thr kinases, has been related to an increase in prostate cancer levels. For this reason, the aim of this study was to evaluate the theoretical interaction of some quinolone derivatives (compounds 1-19) with RSK-4 using 6rv2 protein and RSK-14 inhibitor (LJH685) in a docking model. The results showed that some quinolone derivatives (12, 15, 17, and 18) could interact with the 6rv2 protein surface in a different manner than LJH685. This phenomenon could be translated as greater RSK-14 inhibition, resulting in a decrease in prostate cancer levels. Analyzing these data, these quinolone derivatives could be considered good compounds to treat prostate cancer.
Background Some studies show that some Dibenzo derivatives can produce changes in the cardiovascular system; however, its molecular mechanism is not very clear. Objective The objective of this investigation was to evaluate the inotropic activity of ten Dibenzo derivatives (compounds 1 to 10) on either perfusion pressure or left ventricular pressure. Methods Biological activity produced by the Dibenzo derivatives on either perfusion pressure or coronary resistance was evaluated using an isolated rat heart. In addition, the molecular mechanism of biological activity produced by compound 4 (Dibenzo[b,e]thiophene-11(6H)-one) on left ventricular pressure was determined using both Bay-k8644 and nifedipine as pharmacological tools in an isolated rat heart model. Results The results showed that Dibenzo[b,e]thiophene-11(6H)-one increases perfusion pressure and coronary resistance at a dose of 0.001 nM. Besides, other data display that Dibenzo[b,e]thiophene-11(6H)-one increases left ventricular pressure in a dose-dependent manner (0.001 to 100 nM) and this effect was similar to biological activity produced by Bay-k8644 drug on left ventricular pressure. However, the effect exerted by Dibenzo[b,e]thiophene-11(6H)-one was inhibited in the presence of nifedipine at a dose of 1 nM. Conclusions All these data suggest that Dibenzo[b,e]thiophene-11(6H)-one increase left ventricular pressure through calcium channel activation. In this way, Dibenzo[b,e]thiophene-11(6H)-one could be a good candidate as positive inotropic agent to heart failure.
For several years ago, several epoxide derivatives have been prepared using different methods; however, some protocols use reagents which could be expensive and require specials conditions. The aim of this investigation was to prepare two new epoxide‐derivatives from 3‐ethynylaniline using some reactions such as oximation, acetylation, 2 + 2 addition, functionalized chloroamides, and epoxidation via Darzens reaction. The chemical characteristics of epoxide derivatives were determinate through a spectroscopic and spectrometric analysis. In conclusion, it is noteworthy that the reactions used in this study do not involve expensive reagents or special conditions for the synthesis of epoxide derivatives.
There are several drugs to treat cancer; nevertheless, some can produce adverse effects, such as hypertension, hepatic injury, and erectile dysfunction. In the search for new therapeutic alternatives, some Dibenzo derivatives have been used for treating cancer; however, other data suggest that Dibenzo derivatives can increase this clinical pathology. All these data are confusing; perhaps this phenomenon is due to the different chemical structures of each Dibenzo-derivative. Analyzing this data, this research aimed to evaluate the possible interaction of some Dibenzo derivatives (compounds 1 to 15) on some biomolecules involved in prostate cancer, such as androgen receptor and 5α-reductase enzyme using flutamide, dutasteride, and finasteride drugs as theoretical tools in a Docking model. The results showed that some Dibenzo derivatives (9, 11, and 15) could interact with the androgen receptor surface. Besides, the Dibenzo derivatives 2, 5, and 13 may interact with the 5α-reductase enzyme surface. In conclusion, these data suggest that some Dibenzo derivatives could be good candidates for the treatment of prostate cancer.
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