Biodiversity and Bioactive Potential of Actinomycetes from Unexplored High Altitude Regions of Kargil, India.

The effectiveness of currently available antimicrobials and anticancer medications is steadily declining due to the emergence of drug resistance. Since actinobacteria are important producers of bioactive substances, we have isolated them from the soil samples of exotic North-Western Himalayan terrains. Out of 128 isolates, 39 strains were prioritized based on their bioactive potential. The diversity analysis revealed higher abundance distribution of actinomycetes in the soil of an open field (68.7%), followed by the mountainside (34.9%), from which most of the bioactive strains were obtained. The extract of the strain S26-11 was found to be highly active against Gram-positive Staphylococcus aureus and Bacillus subtilis with a MIC of 0.5 µg/mL and 1 µg/mL respectively. A cytotoxicity assay (sulforhodamine B) was performed on a series of cancer cell lines (PC-3, MCF-7, A-549, and HCT-116). The extract of the strain S26-11 showed cytotoxic activity against all cancer cell lines with an IC50 of 2 µg/mL against PC-3, 1.9 µg/mL against MCF-7, 0.52 µg/mL against A-549, and 0.83 µg/mL against HCT-116. Moreover, the antioxidant activity was assessed using a DPPH-based assay and the results revealed that the S17-8 isolate showed the highest antioxidant activity with IC50 of 114.136 µg/mL. The Response Surface Methodology (RSM) had helped to optimize the physical parameters for scaling up of the bioactive strain S26-11. The unexplored soil niches of Kargil (UT, Ladakh), India, is rich in actinomycetes which are having potential bioactivities, would be worth to explore for the discovery of bioactive compounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01133-1.

Antimicrobial, antibiofilm, docking, DFT and molecular dynamics studies on click-derived isatin-thiosemicarbazone-1,2,3-triazoles.

In an effort to develop new antimicrobial and antibiofilm agents, we have designed and synthesized a novel class of isatin-thiosemicarbazone-1,2,3-triazoles through the CuAAC approach. All the synthesized hybrids were characterized by several spectral techniques such as FTIR, 1H NMR, 13C NMR, 2D NMR and HRMS. All the derivatives were evaluated for their antimicrobial and antibiofilm efficacy towards various microbial species. Triazole hybrid 8d exhibited the highest efficacy towards E. coli (MIC = 0.0067 µmol/mL) and S. aureus (MIC = 0.0067 µmol/mL), whereas, compounds 8b, 8c, 8d, 8e, 9a and terminal alkyne (10) significantly inhibited biofilm formation against S. aureus, B. subtilis and E. coli. To find out the structure-activity relationship and binding interactions of synthesized hybrids with enzymes 1KZN and 5TZ1, molecular docking for all the synthesized hybrids was carried out. DFT calculations for all hybrids and the molecular dynamics studies for compounds 9e and 9f were also performed to support the biological behavior of these hybrids.Communicated by Ramaswamy H. Sarma.

Fabrication, characterization, and interventions of protein, polysaccharide and lipid-based nanoemulsions in food and nutraceutical delivery applications: A review.

The fabrication and application of nanoemulsions for incorporating and delivering diverse bioactive compounds, particularly hydrophobic substances, is becoming an increasing focus of research with the potential to improve the nutritional and health status of individuals. Constant advancements in nanotechnological approaches aid in the creation of nanoemulsions using diverse biopolymers such as proteins, peptides, polysaccharides, and lipids to improve the stability, bioactivity, and bioavailability of active hydrophilic and lipophilic compounds. This article provides a comprehensive overview of various techniques used to create and characterize nanoemulsions as well as theories for understanding their stability. The article also highlights the advancement of nanoemulsions in boosting the bioaccessibility of nutraceuticals to help advance their potential use in various food and pharmaceutical formulations.

Correction to "LC-PDA-MS/MS-Based Dereplication Guided Isolation of a New Optical Isomer of 19,20-Epoxycytochalasin-N and Its Cytotoxic Activity".

[This corrects the article DOI: 10.1021/acsomega.2c03037.].

Synthesis, antimicrobial, antibiofilm and computational studies of isatin-semicarbazone tethered 1,2,3-triazoles.

In present era, heterocyclic compounds containing two or three nitrogen atoms play a vital role in drug discovery. In this context, a new class of isatin-semicarbazone tethered 1,2,3-triazole hybrids was synthesized via Cu(I)-mediated azide alkyne cycloaddition reaction. Structural characteristics of the newly derived compounds were identified by various spectral techniques like FTIR, 1H NMR, 13C NMR, HRMS and single crystal X-ray crystallography. Synthesized derivatives were also screened for in vitro antimicrobial and antibiofilm activity against different microbial species. Triazole hybrid 7e showed significant efficacy towards E. coli having MIC of 0.0063 µmol/mL, whereas 6a, 6b, 7a, 7c, 7e, and 7f showed highest percentage of biofilm inhibition against P. aeruginosa. Bioassay results suggested that these triazole hybrids could act as biomaterial for antimicrobial and antibiofilm applications and may constitute a new promising class of antimicrobial and antibiofilm agents. These results were further supported by in silico docking, DFT calculations and ADME studies.

LC-PDA-MS/MS-Based Dereplication Guided Isolation of a New Optical Isomer of 19,20-Epoxycytochalasin-N and Its Cytotoxic Activity.

The Rosellinia sanctae-cruciana extract was subjected to detailed liquid chromatography tandem mass spectrometry studies. A total of 38 peaks were annotated to m/z 508.26, m/z 510.28, m/z 524.26, m/z 526.28, m/z 540.26, m/z 542.27, and m/z 584.28 [M + H]+. The accurate mass, mutually supported UV/vis spectra, and database search identified these compounds as cytochalasins. Systematic dereplication helped identify a peak at m/z 540.26 [M + H]+ as the new compound. Further, the identified compound was purified by high-performance liquid chromatography and characterized by 2D NMR to be 19,20-epoxycytochalasin N1, a new optical isomer of 19,20-epoxycytochalasin-N. It exhibited substantial cytotoxicity with IC50 values ranging from 1.34 to 19.02 µM. This study shows a fast approach for dereplicating and identifying novel cytochalasin metabolites in crude extracts.

Synergistic Action of Immunotherapy and Nanotherapy against Cancer Patients Infected with SARS-CoV-2 and the Use of Artificial Intelligence.

Since 2019, the SARS-CoV-2 pandemic has caused a huge chaos throughout the world and the major threat has been possessed by the immune-compromised individuals involving the cancer patients; their weakened immune response makes them vulnerable and susceptible to the virus. The oncologists as well as their patients are facing many problems for their treatment sessions as they need to postpone their surgery, chemotherapy, or radiotherapy. The approach that could be adopted especially for the cancer patients is the amalgamation of immunotherapy and nanotherapy which can reduce the burden on the healthcare at this peak time of the infection. There is also a need to predict or analyze the data of cancer patients who are at a severe risk of being exposed to an infection in order to reduce the mortality rate. The use of artificial intelligence (AI) could be incorporated where the real time data will be available to the physicians according to the different patient's clinical characteristics and their past treatments. With this data, it will become easier for them to modify or replace the treatment to increase the efficacy against the infection. The combination of an immunotherapy and nanotherapy will be targeted to treat the cancer patients diagnosed with SARS-CoV-2 and the AI will act as icing on the cake to monitor, predict and analyze the data of the patients to improve the treatment regime for the most vulnerable patients.

Toxicological analysis of synthetic dye orange red on expression of NFκB-mediated inflammatory markers in Wistar rats.

Orange red is a food and cosmetic coloring agent made by the amalgamation of two azo dyes carmoisine and sunset yellow. The current study demonstrates the effect of different concentrations of orange red on antioxidant status, inflammatory biomarkers (TNFα, IFNγ, IL1ß, IL6, COX-2, iNOS, and NFκB/p65), biochemical enzymes, and liver histology. In totality, 25 male Wistar rats were procured and arbitrarily alienated into 5 different groups each with 5 animals. Group I was taken as the control. Groups II-V were designated as treatment groups. Groups II and III were administered with (5 and 25 mg/kg b.wt.) and groups IV and V with (150 and 300 mg/kg b.wt.) of orange red via oral gavage for 30 days. It was observed that both low and high concentrations of orange red (25, 150, and 300 mg/kg) remarkably augmented the levels of serum inflammatory cytokines (TNFα, IFNγ, IL1ß, and IL6) and the protein and gene expression of COX-2, iNOS, and NFκB/p65. A significant decrease in glutathione reductase, glutathione peroxidase, glutathione-S-transferase, superoxidase dismutase, and catalase activity was observed with increasing concentration of orange red. Furthermore, an increase in the level of several vital biochemical parameters and damage severity to hepatic tissue was also found dose dependent.