A Perspective on Therapeutic Applications and Strategies to Mitigate Toxicity of Metallic Nanoparticles.

Metallic nanoparticles (MNPs) have been widely used for diagnostic and therapeutic purposes in clinical practice. A number of MNP formulations are being investigated in clinical trials for various applications. This increase in the use of NPs results in higher exposure to humans, leading to toxicity issues. Hence, it is necessary to determine the possible undesirable effects of the MNPs after in-vivo application and exposure. One of the main reasons for the toxicity of MNPs is the release of their respective metallic ions throughout the body. Many research studies are in progress investigating the various strategies to reduce the toxicity of MNPs. These research studies aim to change the size, dose, agglomeration, release, and excretion rates of MNPs. In this perspective review, we discussed the possible strategies to improve the therapeutic effects of MNPs through various processes, with lessons learned from the studies involving silver nanoparticles (AgNPs). We also discussed the ways to manage the toxicity of MNPs by purification, surface functionalization, synergistic effect, and targeted therapy approach. All these strategies could reduce the dose of the MNPs without compromising their therapeutic benefits, which could decrease the toxicity of MNPs. Additionally, we briefly discussed the market and toxicology testing for FDA-regulated MNPs.

Molecular docking and identification of G-protein-coupled receptor 120 (GPR120) agonists as SARS COVID-19 MPro inhibitors.

COVID-19 has become a pandemic, and any new drug for treating the disease could save millions of lives. Several drugs already in use for other diseases and medical conditions are repurposed for treating COVID-19 in an attempt to find treatment for the disease without spending research time on ADME TOX and other studies on side effects. In this exercise, the drugs repurposed are from antiviral, antibiotics, antiviral for HIV and HCV, anti-cancer, natural medicines, etc. Possible repurposing anti-diabetic GPR-120 agonists used as for SAR-CoV-2 is attempted in the study by carrying out docking of 68 GPR-120 agonists. Ten of these compounds were found to have docking scores -8.3 to -8.0, and the best docking score was observed for an arylsulfonamide and a biarylpropanoic acid belonging to GPR120 agonists previously evaluated for the treatment of type II diabetes. These GPR120 agonists could serve as start point for novel inhibitors for the discovery of drugs to treat COVID-19.

Particle size influence on the composition of sugars in corncob hemicellulose hydrolysate for xylose fermentation by Meyerozyma caribbica.

The xylitol production was performed with acidophilic Meyerozyma caribbica. The particle size of 0.02 ± 0.01 to 0.1 ± 0.05 mm was rich in glucose (12.0 ± 0.5 g/L), whereas 0.5 ± 0.25 to 2.0 ± 0.5 mm had a high content of xylose (8.0 ± 0.5 g/L). The xylitol production in the synthetic, non-detoxified and detoxified hydrolysate media was studied (50 ± 0.5 g/L) using 10% v/v non - induced cells of M. caribbica for 120 h. At the end of fermentation with the specific growth rate of 0.056 ± 0.01 (µ), xylitol yields of 45.00 ± 1.00%, 10.00 ± 1.00% and 54.00 ± 1.00% were obtained. The detoxification of the hydrolysate prepared using an identified corncob particle size of 0.5 ± 0.25 to 2.0 ± 0.5 mm could be used as the prospective pretreatment process for ecofriendly and industrial scale production of xylitol with M. caribbica.

In situ conservation of endangered tree species (Elaeocarpus venustus Bedd.) habitated in Agasthiyamalai Biosphere Reserve, Southern Western Ghats, India.

Elaeocarpus venustus is an endemic as well as endangered tree species habitated in the wet evergreen forests of Southern Western Ghats (SWG), India. Due to insufficient natural regeneration, low seedling tendency, and prevailing anthropogenic disturbances, their distribution has been shrinking in their native environment. Towards conserving this endangered species, we have attempted to propagate E. venustus in its habitat by adopting vegetative propagation techniques of cutting and air layering through growth hormones. Significant growth has been observed by providing 2 mM concentration of indole-3-butyric acid (IBA) for both cutting and air layering. Higher rooting response has been observed through cutting and air layering techniques during monsoon periods. Based on the results of the study, we suggest that the cutting and air layering techniques can be employed as promising strategies towards the in situ conservation and promotion of Elaeocarpus venustus tree species as well as other endangered species in Western Ghats.

Cytotoxicity and Synergistic Effect of Biogenically Synthesized Ternary Therapeutic Nano Conjugates Comprising Plant Active Principle, Silver and Anticancer Drug on MDA-MB-453 Breast Cancer Cell Line.

Drug delivery through biogenically synthesized silver nanoparticles (AgNPs) in cancer treatment is exerted by smaller size entailing high surface area and synergistic effects of embedded biomolecules.  In this study, prepared ternary conjugates of silver with plant active compound and anticancer drug towards reducing the dose through synergy, rendered by Electrostatic Attraction (EA) of functionalized drug on to the surface of biogenically synthesized AgNPs. The biogenic synthesis resulted in particles of nanometer range as well as serving reducing and capping agents. The cytotoxicity and synergistic effect of ternary therapeutic nano conjugates evaluated using MDA-MB-453 breast cancer cells were found to be superior than Doxorubicin (Dox). Quantitative HPTLC analysis showed 57.22 % inhibition by Dox-AP-AgNPs at a concentration of 2.5 µg/mL of Andrographolide and 0.95 µg/mL of Dox validating synergistic effect of the ternary conjugate.

Isolation and in silico evaluation of antidiabetic molecules of Cynodon dactylon (L.).

Cynodon dactylon is a potential source of metabolites such as flavanoids, alkaloids, glycosides and ß-sitosterol and has been traditionally employed to treat urinary tract and other microbial infections and dysentery. The present work attempts to evaluate the activity of C. dactylon extracts for glycemic control. Aqueous extracts of C. dactylon analyzed by HPLC-ESI MS have identified the presence of apigenin, luteolin, 6-C-pentosyl-8-C-hexosyl apigenin and 6-C-hexosyl-8-C-pentosyl luteolin. Evaluation of hypoglycemic activity through an extensive in silico docking approach with PPARγ (Peroxisome Proliferator-Activated Receptor), GLUT-4 (glucose transporter-4) and SGLT2 (sodium glucose co-transporter-2) revealed that luteolin, apigenin, 6-C-pentosyl-8-C-hexosyl apigenin, 6-C-hexosyl-8-C-pentosyl luteolin interact with SGLT2. Interactions of these molecules with Gln 295 and Asp 294 residues of SGLT2 have been shown to compare well with that of the phase III drug, dapagliflozin. These residues have been proven to be responsible for sugar sensing and transport. This work establishes C. dactylon extract as a potential SGLT2 inhibitor for diabetic neuropathy thus enabling a possibility of this plant extract as a new alternative to existing diabetic approaches.

Efficient and stereodivergent synthesis of deoxyimino sugars.

Both cis- and trans-2-substituted-1,2,3,6-tetrahydro-pyridin-3-ols have been prepared via an aldol condensation-ring-closing metathesis sequence. A stereodivergent synthesis of optionally functionalized deoxyimino sugars was achieved via asymmetric dihydroxylation or epoxidation/nucleophilic substitution of these tetrahydropyridines.