ABSTRACT
The trypanothione reductase enzyme, which neutralizes the reactive oxygen species produced inside the macrophages to kill the parasites, is one of the evasion strategies Leishmania uses to survive inside the cells. The vitality of the parasite depends on Leishmania major trypanothione reductase (LmTr), a NADPH-dependent flavoprotein oxidoreductase essential for thiol metabolism. Since this enzyme is distinct and lacking in humans, we focused on it in our study to screen for new inhibitors to combat leishmaniasis. Using the I-TASSER server, a three-dimensional model of LmTr was generated. The Autodock vina program was used in high-throughput virtual screening of the ZINC database. The top seven molecules were ranked according to their binding affinity. The compounds with the highest binding affinities and the right number of hydrogen bonds were chosen. These compounds may be effective at inhibiting the target enzyme's (LmTr) activity, making them new leishmaniasis treatments. These compounds may serve as a useful starting point for a hit-to-lead approach in the quest for new anti-Leishmania drugs that are more efficient and less cytotoxic. The average node degree is 5.09, the average local clustering coefficient is 0.868, and the PPI enrichment p-value is 8.9e-06, indicating that it is sufficiently connected to regulate the network. TRYR (LmTr protein) also interacts physically with ten additional proteins in the pathogenesis network. The findings of the study indicated that successfully suppressing the LmTr protein in vitro and in vivo may finally result in regulating the L. major pathogenesis.Communicated by Ramaswamy H. Sarma.
ABSTRACT
The genesis of cancer is a precisely organized process in which normal cells undergo genetic alterations that cause the cells to multiply abnormally, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain. Potential drugs that could modify these carcinogenic pathways are the ones that will be used in clinical trials as anti-cancer drugs. Resveratrol (RES) is a polyphenolic natural antitoxin that has been utilized for the treatment of several diseases, owing to its ability to scavenge free radicals, control the expression and activity of antioxidant enzymes, and have effects on inflammation, cancer, aging, diabetes, and cardioprotection. Although RES has a variety of pharmacological uses and shows promising applications in natural medicine, its unpredictable pharmacokinetics compromise its therapeutic efficacy and prevent its use in clinical settings. RES has been encapsulated into various nanocarriers, such as liposomes, polymeric nanoparticles, lipidic nanocarriers, and inorganic nanoparticles, to address these issues. These nanocarriers can modulate drug release, increase bioavailability, and reach therapeutically relevant plasma concentrations. Studies on resveratrol-rich nano-formulations in various cancer types are compiled in the current article. Studies relating to enhanced drug stability, increased therapeutic potential in terms of pharmacokinetics and pharmacodynamics, and reduced toxicity to cells and tissues are the main topics of this research. To keep the readers informed about the current state of resveratrol nano-formulations from an industrial perspective, some recent and significant patent literature has also been provided. Here, the prospects for nano-formulations are briefly discussed, along with machine learning and pharmacometrics methods for resolving resveratrol's pharmacokinetic concerns.