Paclitaxel: Application in Modern Oncology and Nanomedicine-Based Cancer Therapy

Paclitaxel is a broad-spectrum anticancer compound, which was derived mainly from a medicinal plant, in particular, from the bark of the yew tree Taxus brevifolia Nutt. It is a representative of a class of diterpene taxanes, which are nowadays used as the most common chemotherapeutic agent against many forms of cancer. It possesses scientifically proven anticancer activity against, e.g., ovarian, lung, and breast cancers. The application of this compound is difficult because of limited solubility, recrystalization upon dilution, and cosolvent-induced toxicity. In these cases, nanotechnology and nanoparticles provide certain advantages such as increased drug half-life, lowered toxicity, and specific and selective delivery over free drugs. Nanodrugs possess the capability to buildup in the tissue which might be linked to enhanced permeability and retention as well as enhanced antitumour influence possessing minimal toxicity in normal tissues. This article presents information about paclitaxel, its chemical structure, formulations, mechanism of action, and toxicity. Attention is drawn on nanotechnology, the usefulness of nanoparticles containing paclitaxel, its opportunities, and also future perspective. This review article is aimed at summarizing the current state of continuous pharmaceutical development and employment of nanotechnology in the enhancement of the pharmacokinetic and pharmacodynamic features of paclitaxel as a chemotherapeutic agent

Cold Tolerance Mechanisms in Mungbean (<i>Vigna radiata</i> L.) Genotypes during Germination

Mungbean or greengram (Vigna radiata) is an important legume crop well known for its high protein with nitrogen-fixing abilities. However, the severe yield loss in mungbean occurs due to susceptibility to low temperatures at all stages of plant growth including germination and is a serious concern for its cultivation and productivity. To select cold-tolerant genotypes, a germination-based screening at 10 °C was performed in a total of 204 germplasms. The study showed that cold stress of the initial 8-days during seedling establishment imposed a negative impact throughout the life of mungbean genotypes, which were reflected in the vegetative and reproductive phase (plant height, days to 50% flowering and pods/plant, seeds/pod, yield/plant, and 100-seed weight). The biplot analysis showed that parameters such as germination rate index, Timson’s index, mean germination time, and coefficient of the velocity of germination are the key influential germination parameters for identifying cold tolerance in the seedling stage. Identified cold-tolerant genotype (PAU911) retained higher rootlet number, leaf area, and increased chlorophyll, carotenoid, and malondialdehyde (MDA) content at 10 °C. Based on the confocal microscopic study, it is noticed that the stomatal density, open pore percentage, and trichome density were significant differences in seedlings exposed to cold stress as compared to non-stress. On the basis of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) analysis, it is observed that a new protein identified as TETRATRICOPEPTIDE-REPEAT THIOREDOXIN-LIKE1 (TTL1) (UNIPROT Identifier: LOC106762419) which highly correlated with the cold stress response of in the cold-tolerant genotype. Our study identifies a noble member, TTL1, whose expression has a positive role in cold tolerance response at the protein level in V. radiata. This study will help breeding programs with regard to the sustainable growth of mungbean

Nature Potential for COVID-19: Targeting SARS-CoV-2 Mpro Inhibitor with Bioactive Compound

Corona viruses were first identified in 1931 and SARS-CoV-2 is the most recent. COVID-19 is a pandemic that put most of the world on lockdown and the search for therapeutic drugs is still on-going. Therefore, this study uses in silico screening to identify natural bioactive compounds from fruits, herbaceous plants and marine invertebrates that are able to inhibit protease activity in SARS-CoV-2(PDB: 6LU7). We have used various screening strategies such as drug likeliness, antiviral activity value prediction, molecular docking, ADME (absorption, distribution, metabolism, and excretion), molecular dynamics (MD) simulation and MM/GBSA (molecular mechanics/generalized born and surface area continuum solvation). 17 compounds were shortlisted using Lipinski’s rule. 5 compounds revealed significantly good predicted antiviral activity values and out of them only 2 compounds, Macrolactin A and Stachyflin, showed good binding energy values of -9.22 and -8.00 kcal/mol within the binding pocket, catalytic residues (HIS 41 and CYS 145) of Mpro. These two compounds were further analyzed for their ADME properties. The ADME evaluation of these 2 compounds suggested that they could be effective as therapeutic agents for developing drugs for clinical trials. MD simulations showed that protein-ligand complexes of Macrolactin A and Stachyflin were stable for 100 nano seconds. The MM/GBSA calculations of Mpro – Macrolactin A complex indicated higher binding free energy (-42.58 ± 6.35 kcal/mol) with Mpro protein target receptor (6LU7). DCCM and PCA analysis on the residual movement in the MD trajectories confirmed the good stability on Macrolactin A bound state of 6LU7. This signify the stable conformation of 6LU7 with high binding energy with Macrolactin A. Thus, this study showed that Macrolactin A could be an effective therapeutical agent for SARS-CoV-2protease (6LU7) inhibition. Additional in vitro and in vivo validations are needed to determine efficacy and dose of Macrolactin A in biological systems.</p

Macrolactin A as a novel inhibitory agent for SARS-CoV-2 Mpro: bioinformatics approach

COVID-19 is a disease that puts most of the world on lockdown and the search for therapeutic drugs is still ongoing. Therefore, this study used in silico screening to identify natural bioactive compounds from fruits, herbaceous plants, and marine invertebrates that are able to inhibit protease activity in SARS-CoV-2 (PDB: 6LU7). We have used extensive screening strategies such as drug likeliness, antiviral activity value prediction, molecular docking, ADME, molecular dynamics (MD) simulation, and MM/GBSA. A total of 17 compounds were shortlisted using Lipinski’s rule in which 5 compounds showed significant predicted antiviral activity values. Among these 5, only 2 compounds, Macrolactin A and Stachyflin, showed good binding energy of −9.22 and −8.00 kcal/mol, respectively, within the binding pocket of the Mpro catalytic residues (HIS 41 and CYS 145). These two compounds were further analyzed to determine their ADME properties. The ADME evaluation of these 2 compounds suggested that they could be effective in developing therapeutic drugs to be used in clinical trials. MD simulations showed that protein–ligand complexes of Macrolactin A and Stachyflin with the target receptor (6LU7) were stable for 100 nanoseconds. The MM/GBSA calculations of Mpro–Macrolactin A complex indicated higher binding free energy (−42.58 ± 6.35 kcal/mol). Dynamic cross-correlation matrix (DCCM) and principal component analysis (PCA) on the residual movement in the MD trajectories further confirmed the stability of Macrolactin A bound state with 6LU7. In conclusion, this study showed that marine natural compound Macrolactin A could be an effective therapeutic inhibitor against SARS-CoV-2 protease (6LU7). Additional in vitro and in vivo validations are strongly needed to determine the efficacy and therapeutic dose of Macrolactin A in biological systems