Mini reviews in medicinal chemistry最新文献

Levothyroxine or l-thyroxine is artificially manufactured thyroxine, which is used as a drug to treat underactive thyroid conditions in humans. The drug, levothyroxine, is consumed daily in a prescribed dose to replace the missing thyroid hormone thyroxine in an individual with an underactive thyroid, and it helps to maintain normal physiological conditions. Though it is a life-maintaining drug, it replaces the missing thyroid hormone and performs the necessary daily metabolic functions in our body. Like all other allopathic drugs, it comes with certain side effects, which include joint pain, cramps in muscle, weight gain/loss, hair loss, etc. The thyroid hormone, thyroxine, is known to mobilize fat in our body, including the ones from the hepatic system. An underactive thyroid may cause an accumulation of fat in the liver, leading to a fatty liver, which is clinically termed Non-Alcoholic Fatty Liver Disease (NAFLD). The correlation between hypothyroidism and NAFLD is now well-studied and recognized. As levothyroxine performs the functions of the missing thyroxine, it is anticipated, based on certain preliminary studies, that the drug helps to mobilize hepatic fat and thus may have a crucial role in mitigating the condition of NAFDL.

Rational predictions on binding kinetics parameters of drugs to targets play significant roles in future drug designs. Full conformational samplings of targets are requisite for accurate predictions of binding kinetic parameters. In this review, we mainly focus on the applications of enhanced sampling technologies in calculations of binding kinetics parameters and residence time of drugs. The methods involved in molecular dynamics simulations are applied to not only probe conformational changes of targets but also reveal calculations of residence time that is significant for drug efficiency. For this review, special attention are paid to accelerated molecular dynamics (aMD) and Gaussian aMD (GaMD) simulations that have been adopted to predict the association or disassociation rate constant. We also expect that this review can provide useful information for future drug design.

Since ferroptosis was reported in 2012, its application prospects in various diseases have been widely considered, initially as a treatment direction for tumors. Recent studies have shown that ferroptosis is closely related to the occurrence and development of atherosclerosis. The primary mechanism is to affect the occurrence and development of atherosclerosis through intracellular iron homeostasis, ROS and lipid peroxide production and metabolism, and a variety of intracellular signaling pathways. Inhibition of ferroptosis is effective in inhibiting the development of atherosclerosis, and it can bring a new direction for treating atherosclerosis. In this review, we discuss the mechanism of ferroptosis and focus on the relationship between ferroptosis and atherosclerosis, summarize the different types of ferroptosis inhibitors that have been widely studied, and discuss some issues worthy of attention in the treatment of atherosclerosis by targeting ferroptosis.

A category of cytoplasmic transcription factors called STATs mediates intracellular signaling, which is frequently generated at receptors on cell surfaces and subsequently sent to the nucleus. STAT3 is a member of a responsible for a variety of human tumor forms, including lymphomas, hematological malignancies, leukemias, multiple myeloma and several solid tumor types. Numerous investigations have demonstrated constitutive STAT3 activation lead to cancer development such as breast, head and neck, lung, colorectal, ovarian, gastric, hepatocellular, and prostate cancers. It's possible to get a hold of the book here. Tumor cells undergo apoptosis when STAT3 activation is suppressed. This review highlights the STAT3 activation and inhibition which can be used for further studies.

Drug discovery, vaccine design, and protein interaction studies are rapidly moving toward the routine use of molecular dynamics simulations (MDS) and related methods. As a result of MDS, it is possible to gain insights into the dynamics and function of identified drug targets, antibody-antigen interactions, potential vaccine candidates, intrinsically disordered proteins, and essential proteins. The MDS appears to be used in all possible ways in combating diseases such as cancer, however, it has not been well documented as to how effectively it is applied to infectious diseases such as Leishmaniasis. As a result, this review aims to survey the application of MDS in combating leishmaniasis. We have systematically collected articles that illustrate the implementation of MDS in drug discovery, vaccine development, and structural studies related to Leishmaniasis. Of all the articles reviewed, we identified that only a limited number of studies focused on the development of vaccines against Leishmaniasis through MDS. Also, the PCA and FEL studies were not carried out in most of the studies. These two were globally accepted utilities to understand the conformational changes and hence it is recommended that this analysis should be taken up in similar approaches in the future.