Pharmacokinetic studies, molecular docking, and molecular dynamics simulations of phytochemicals from Morus alba: a multi receptor approach for potential therapeutic agents in colorectal cancer.

This study explores the therapeutic potential of phytochemicals derived from Morus alba for colorectal cancer (CRC) treatment. Colorectal cancer is a global health concern with increasing mortality rates, necessitating innovative strategies for prevention and therapy. Employing in silico analysis, molecular docking techniques (MDT), and molecular dynamics simulations (MDS), the study investigates the interactions between Morus alba-derived phytochemicals and key proteins (AKT1, Src, STAT3, EGFR) implicated in CRC progression. ADME/T analysis screens 78 phytochemicals for drug-like and pharmacokinetic properties. The study integrates Lipinski's Rule of Five and comprehensive bioactivity assessments, providing a nuanced understanding of Morus alba phytoconstituent's potential as CRC therapeutic agents. Notably, 14 phytochemicals out of 78 emerge as potential candidates, demonstrating oral bioavailability and favorable bioactivity scores. Autodock 1.5.7 is employed for energy minimization followed by molecular docking with the highest binding energy observed to be - 11.7 kcal/mol exhibited by Kuwanon A against AKT1. Molecular dynamics simulations and trajectory path analysis were conducted between Kuwanon A and AKT1 at the Pleckstrin homology (PH) domain region (TRP80), revealing minimal deviations. In comparison to the standard drug Capivasertib, the phytochemical Kuwanon A emerges as a standout candidate based on computational analysis. This suggests its potential as an alternative to mitigate the limitations associated with the standard drug. The research aims to provide insights for future experimental validations and to stimulate the development of Kuwanon A as a novel, effective therapeutic agent for managing colorectal cancer.

A comprehensive review of biosurfactant production and its uses in the pharmaceutical industry.

Biosurfactants are naturally occurring, surface-active chemicals generated by microorganisms and have attracted interest recently because of their numerous industrial uses. Compared to their chemical equivalents, they exhibit qualities that include lower toxic levels, increased biodegradable properties, and unique physiochemical properties. Due to these traits, biosurfactants have become attractive substitutes for synthetic surfactants in the pharmaceutical industry. In-depth research has been done in the last few decades, demonstrating their vast use in various industries. This review article includes a thorough description of the various types of biosurfactants and their production processes. The production process discussed here is from oil-contaminated waste, agro-industrial waste, dairy, and sugar industry waste, and also how biosurfactants can be produced from animal fat. Various purification methods such as ultrafiltration, liquid-liquid extraction, acid precipitation, foam fraction, and adsorption are required to acquire a purified product, which is necessary in the pharmaceutical industry, are also discussed here. Alternative ways for large-scale production of biosurfactants using different statistical experimental designs such as CCD, ANN, and RSM are described here. Several uses of biosurfactants, including drug delivery systems, antibacterial and antifungal agents, wound healing, and cancer therapy, are discussed. Additionally, in this review, the future challenges and aspects of biosurfactant utilization in the pharmaceutical industry and how to overcome them are also discussed.

Protease inhibitors as a potential agent against visceral Leishmaniasis: A review to inspire future study

Abstract Leishmaniasis is transmitted by sandfly which carries the intracellular protozoa in their midgut. Among visceral, cutaneous and mucocutaneous leishmaniasis, visceral type that is caused by Leishmania donovani is the most lethal one. Findings of leishmanial structure and species took place in 19th century and was initiated by Donovan. Leishmaniasis is still a major concern of health issues in many endemic countries in Asia, Africa, the Americas, and the Mediterranean region. Worldwide1.5-2 million new cases of cutaneous leishmaniasis and 500,000 cases of visceral leishmaniasis are reported each year. Leishmaniasis is endemic in nearly 90 countries worldwide and close to 12 million new cases of leishmaniasis are reported worldwide annually. Studies on antileishmanial drug development is of major concern as leishmaniasis are the second largest parasitic killer in the world and the available drugs are either toxic or costly. The major surface GP63 protease, also known as Zinc- metalloproteases present on the surface of leishmanial promastigotes, can be targeted for drug development. Protease inhibitors targeting such surface proteases show promising results. Different protease inhibitors have been isolated from marine actinobacteria against many infectious diseases. Metabolites produced by these actinobacteria may have greater importance for the discovery and development of new antileishmanial drugs. Hence, this review discusses the background, current situation, treatment, and protease inhibitors from marine actinobacteria for drug development against GP63 molecules.

An ex-situ and in vitro approach towards the bioremediation of carcinogenic hexavalent chromium.

Chromium, ranking the second most among toxic heavy metal pollutants in the world, causing respiratory, cardiovascular and renal problems in human beings is under study herein. We examined the biological remediation of the carcinogenic Cr (VI) polluted soils by indigenous yeast isolates. The total element analysis of the treated sample was determined by Energy Dispersion X-ray Micro Analysis (EDXMA). The sample under study was observed to have a high concentration of 458.29 mgKg-1 Cr (VI), determined by Atomic Absorption Spectroscopy (AAS) and DPC analysis. The most tolerant isolate designated as CSR was used for in vitro and ex-situ bioremediation studies of Cr (VI). The isolate achieved significant bioremediation of 86% in vitro and 75.12% in ex-situ method. The optimal conditions for in vitro bioremediation were found to be 28 °C and a pH of 6. The ITS1, 5.8S rRNA and D1, D2 domain of LSU rRNA gene characterization of the isolate CSR illustrated that it belongs to Ustilago genera. The isolate was deposited in NCBI GenBank as Ustilago sp. CSR (KY284846). Although, Ustilago is generally a pathogenic fungus, our study opens up the scope of using Ustilago spp. for bioremediation of the carcinogenic heavy metal Chromium.

Fatty acyl compounds from marine Streptomyces griseoincarnatus strain HK12 against two major bio-film forming nosocomial pathogens; an in vitro and in silico approach.

The perpetual increase in the resistance offered by biofilm-forming nosocomial pathogens has become a critical clinical challenge. Marine Streptomyces sps present a promising future of novel compounds with novel applications. We focus on the anti-biofilm activity of marine Streptomyces against two major nosocomial pathogens from clinical samples, Pseudomonas aeruginosa and Staphylococcus aureus. Herein, Streptomyces griseoincarnatus, a species known to harbour alkaline protease inhibitors and anti-tumour compounds were found to exhibit anti-biofilm activity. The study progresses to decipher the anti-biofilm potential of the extract as 82.657 ±â€¯1.1002% against P. aeruginosa and 78.973 ±â€¯1.672% against S. aureus at 100 µg/mL. The strain under study, S. griseoincarnatus HK 12 (accession no MF100857) has revealed the presence of certain fatty acyl compounds namely, 13Z-Octadecenal, 9Z-Octadecenal, Arachidic acid, Tetracosanoic acid and Erucic acid by GC-MS screening. Furthermore, the active compounds were docked against the quorum sensing system, LasI. The compound 13Z-Octadecenal was found to bind to the conserved sites of substrate binding with a binding energy of -1.90 kcal/mol thus, affirming the inhibitory activity of the fatty acyl compound. These active compounds were previously reported to be a part of active extracts exhibiting relevant antagonistic activities, but this so far is the first time they are found possessing anti-biofilm activity. Interestingly, the toxicity level of the extract at a high concentration of 500 µg/mL is as low as 11.5% when tested against human lung cancer lines, A549. Thus the report highlights the evidence of the potential of S griseoincarnatus HK12 to be an active and safe anti-biofilm agent.

Marine actinobacterial mediated gold nanoparticles synthesis and their antimalarial activity.

Streptomyces sp LK-3 (JF710608) mediated Gold nanoparticles (Au-N-LK3) were found within the size range of 5-50 nm. Au-N-LK3 treatment in Plasmodium berghei ANKA (PbA) infected mice delayed the parasitemia rise (~6%) compared to PbA infection on 8 days post infection. Survivability of mice increases to ~85% in Au-N-LK3 treated mice in contrast to in PbA (~50%) infected mice in 8 dpi with respect to control. During Au-N-LK3 treatment in PbA infection, histomorphological analysis revealed as such no change in spleen and liver tissue during 8 dpi. Our results confirmed up-regulation of TGF-ß and down-regulation of TNF-α in tissue and serum level in PbA infected Au-N-LK3 treated mice compared to PbA infection. No significant changes were found in the hatchability of Artemia embryos upto 8 mg. The results obtained suggest that the Au-N-LK3 possess anti-malarial activity and could be considered as a potential source for anti-malarial drug development. FROM THE CLINICAL EDITOR: These investigators present a method of marine actinobacteria mediated synthesis of gold nanoparticles, resulting in nanoparticles that possess anti-malarial activity and could be considered in future anti-malarial drug development.