Exploring the Pharmacological Potential of the Chemically Characterized Essential Oil from Clinopodium nepeta subsp. ascendens: A Combined In Vitro and In Silico Analysis

This thorough examination explores the various biological characteristics present in the essential oil derived from Clinopodium nepeta subsp. ascendens (CNEO), a subspecies previously unrecognized and indigenous to the eastern part of Morocco. This subspecies is distinguished from C. nepeta by the distinctive feature of having purple or pale pinkish-white flowers. The study initiates with a thorough scrutiny of the phytochemical composition of CNEO via gas chromatography-mass spectrometry (GC-MS), revealing a nuanced spectrum of 24 terpene compounds. Among these, noteworthy constituents such as linalyl acetate (23.28%), Trifluoroacetyl-α-terpineol (13.66%), camphor (13.28%), and menthol (9.22%) are identified. These compounds, acknowledged for their notable biological and pharmacological attributes, serve as focal points for subsequent analyses. Beyond compositional elucidation, the study systematically investigates the diverse biological activities of CNEO. The essential oil exhibits substantial antioxidant potential, as substantiated by robust total antioxidant capacity (TAC) of 315.07 μg AA/mg and effective inhibition of DPPH free radicals (IC50 = 112.97 ± 2.67 µg/ml). Demonstrating promising antibacterial efficacy against various strains, occasionally surpassing gentamicin, positions CNEO as a potential antibacterial agent. Equally notable antifungal efficacy, surpassing that of cycloheximide, with low minimum inhibitory concentrations (MIC) is obtained, underscoring its potent antifungal properties. The antidiabetic potential of CNEO manifests through significant inhibition of xanthine oxidase (IC50 = 30.82 ± 0.78 µg/ml), α-amylase (IC50 = 40.13 ± 1.60 µg/ml), and α-glucosidase (IC50 = 45.30 ± 0.69 µg/ml) activities, suggesting therapeutic prospects in glycemic regulation. Furthermore, the essential oil showcases compelling anti-tyrosinase activity (IC50 = 29.78 ± 1.01 µg/ml), indicating potential dermatoprotective applications in melanin regulation. The implications of these findings provide a robust foundation for future investigations, unraveling the full therapeutic potential of CNEO within medical, cosmetic, and industrial contexts

Immunoinformatics and reverse vaccinology approach in designing a novel highly immunogenic multivalent peptide-based vaccine against the human monkeypox virus

Background: Monkeypox is a highly infectious zoonotic disease, often resulting in complications ranging from respiratory illnesses to vision loss. The escalating global incidence of its cases demands prompt attention, as the absence of a proven post-exposure treatment underscores the criticality of developing an effective vaccine.Methods: Interactions of the viral proteins with TLR2 and TLR4 were investigated to assess their immunogenic potentials. Highly immunogenic proteins were selected and subjected to epitope mapping for identifying B-cell and MHC class I and II epitopes. Epitopes with high antigenicity were chosen, considering global population coverage. A multi-target, multi-epitope vaccine peptide was designed, incorporating a beta-defensin 2 adjuvant, B-cell epitopes, and MHC class I and II epitopes.Results: The coordinate structure of the engineered vaccine was modeled and validated. In addition, its physicochemical properties, antigenicity, allergenicity, and virulence traits were evaluated. Molecular docking studies indicated strong interactions between the vaccine peptide and the TLR2 receptor. Furthermore, molecular dynamics simulations and immune simulation studies reflected its potent cytosolic stability and robust immune response dynamics induced by the vaccine.Conclusion: This study explored an innovative structure-guided approach in the use of immunoinformatics and reverse vaccinology in pursuit of a novel multi-epitope vaccine against the highly immunogenic monkeypox viral proteins. The simulation studies indicated the engineered vaccine candidate to be promising in providing prophylaxis to the monkeypox virus; nevertheless, further in vitro and in vivo investigations are required to prove its efficacy

Phytochemicalanalysis,cytotoxic,antioxidant,andantibacterial activities of lichens

© 2020 Noura Aoussar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Lichens present a complex symbiotic relationship between a filamentous fungus, photoautotrophic partner (algae or cyanobacteria), and bacterial community. The Objective of the Study. This study aimed at investigating the chemical composition and cytotoxic, antioxidant, and antimicrobial activities of acetone extracts of Moroccan Evernia prunastri (E. prunastri), Ramalina farinacea (R. farinacea), and Pseudevernia furfuracea (P. furfuracea). Materials and Methods. The phytochemical analysis was carried out by HPLC-UV. The cytotoxic effect was assessed on human prostate cancer (22RV1), human colon carcinoma (HT-29), human hepatocellular carcinoma (Hep-G2), and Hamster ovarian cancer (CHO) cells lines by WST1 assay. The antioxidant power was assessed by DPPH and FRAP assays. The antibacterial effect was obtained using the broth microdilution method. Results. The findings of phytochemical analysis showed that the lichens studied possess interesting bioactive molecules such as physodalic acid, evernic acid, and usnic acid, as well as protocetraric acid. According to the American National Cancer Institute guidelines, the WST-1 test showed that all crude extracts did not show significant cytotoxic effects against all concerous cell lines, and IC50 values ranged from 42.30 to 140.24 µg/mL. Regarding the antioxidant activity, P. furfuracea extract showed the highest free-radical-scavenging ability (IC50 = 498.40 µg/mL). The most potent antibacterial extract was recorded for P. furfuracea extract with a minimum inhibitory concentration (MIC) ranging from 0.039 to 0.31 mg/mL. Conclusion. In this research work, we report that the studied lichen extracts exhibit an important biological effect, supporting that lichens represent a hopeful source of original natural products for the research of new bioactive molecules having a pharmaceutical interest

Essential Oils from Artemisia herba alba Asso., Maticaria Recutita L., and Dittrichia Viscosa L. (Asteraceae): A Promising Source of Eco-Friendly Agents to Control Callosobruchus maculatus Fab. Warehouse Pest

Callosobruchus maculatus (Fab.) (C. maculatus) is one of the major pests of legume seeds in storage causing significant damage, leading to food insecurity and low income for farmers. This work was planned to develop eco-friendly agents from essential oils of Artemisia herba alba Asso. (AEO), Maticaria Recutita L. (MEO), and Dittrichia Viscosa L. (DEO) to control C. maculatus. To achieve this goal, essential oils (EOs) were extracted by hydro-distillation using Clevenger apparatus before being characterized by GC-MS. EOs were used for testing purposes using three different tests, namely, inhalation toxicity, contact toxicity, and repellency tests. GC-MS analysis of EOs showed the presence of 16 potentially active compounds in AEO and 38 in MEO, whilst 15 compounds were identified in DEO. AEO was higher in thujone (57.6%) and chrysanthenone (11.8%). Santolina alcohol (40.7%) and germacrene D (8.9%) were the major compounds identified in MEO, whereas isocostic acid (72.3%) was the chief compound of DEO. The obtained findings showed that the studied EOs showed considerable insecticidal activity against C. maculatus with a lethal dose (LC50) of 3.78, 8.86, and 14.34 μL/1 liter of air by AEO, MEO, and DEO, respectively. At 1 μL/1 liter of air, the oviposition reduction rate was 90.02%, 70.65%, and 48.23% by AEO, MEO, and DEO, respectively, whereas the emergence reduction rate was 87.32%, 60.08%, and 32.24% by AEO, MEO, and DEO, respectively. With increasing doses up to 20 μL/L, the reduction of individual emergence reached 98.8% by AEO of 24 h after treatment. AEO, MEO, and DEO showed significant repellent effects against adults of C. maculatus with repulsion percentages of 60.83%, 50.83%, and 72.5%, respectively. The outcome of this work suggests that the essential oils of the studied plants, particularly Artemisia herba alba Asso. oils, can constitute a natural and environmentally friendly alternative to develop new bioinsecticides for the control of C. maculatus.</jats:p

Isolation, identification, and characterization of resistant bacteria to antibiotics from pharmaceutical effluent and study of their antibiotic resistance

Pharmaceutical effluents primarily enter aquatic environments through the discharge of treated and untreated wastewater from various sources, including hospitals, pharmaceutical manufacturing facilities, and households. Microbes sourced from pharmaceutical effluents such as Pseudomonas spp. pose a significant public health concern because of their high levels of resistance to multiple drugs and extreme multidrug resistance. Therefore, the present study was conducted for the isolation, identification, and molecular characterization of selected isolates from pharmaceutical effluents and also determined their antibiotic sensitivity patterns. From June 2016 to March 2017, a study was conducted on four well-known pharmaceutical companies specializing in antibiotic production in Dhaka and Gazipur. Four wastewater samples were collected from various origins and then brought to the Bacteriology laboratory for microbiological examination. Twelve pure isolates were obtained and characterized through cultural and biochemical tests while molecular identification of Pseudomonas spp. was performed using the 16S rRNA gene sequence. Twelve commercially available antibiotics were used for antibiotic sensitivity tests using Kirby-Bauer disk diffusion methods. We isolated the most predominant isolates, Pseudomonas aeruginosa (41.67%), followed by Bacillus spp. (33.33%) and Staphylococcus spp. (25%) respectively. Among 12 antibiotics, ciprofloxacin is 100% sensitive against P. aeruginosa, while the remaining 11 antibiotics are 100% resistant. Bacillus spp. showed 100% resistance to all antibiotics while 50% sensitive to vancomycin and 100% to chloramphenicol, respectively. Staphylococcus spp. was 100% resistant to all antibiotics. Our research suggested that P. aeruginosa is the reservoir of antibiotic resistance genes and spreads disease to humans from the environment. The findings of this study, i.e., the isolation, identification, and characterization of antibiotic-resistant bacteria from pharmaceutical effluent have highlighted, comprehended, and mitigated the dissemination of antibiotic resistance and opportunistic bacteria

Mechanistic insight of Staphylococcus aureus associated skin cancer in humans by Santalum album derived phytochemicals: an extensive computational and experimental approaches

An excessive amount of multidrug-resistant Staphylococcus aureus is commonly associated with actinic keratosis (AK) and squamous cell carcinoma (SCC) by secreted virulence products that induced the chronic inflammation leading to skin cancer which is regulated by staphylococcal accessory regulator (SarA). It is worth noting that there is currently no existing published study that reports on the inhibitory activity of phytochemicals derived from Santalum album on the SarA protein through in silico approach. Therefore, our study has been designed to find the potential inhibitors of S. aureus SarA protein from S. album-derived phytochemicals. The molecular docking study was performed targeting the SarA protein of S. aureus, and CID:5280441, CID:162350, and CID: 5281675 compounds showed the highest binding energy with −9.4 kcal/mol, −9.0 kcal/mol, and −8.6 kcal/mol respectively. Further, molecular dynamics simulation revealed that the docked complexes were relatively stable during the 100 ns simulation period whereas the MMPBSA binding free energy proposed that the ligands were sustained with their binding site. All three complexes were found to be similar in distribution with the apoprotein through PCA analysis indicating conformational stability throughout the MD simulation. Moreover, all three compounds’ ADMET profiles revealed positive results, and the AMES test did not show any toxicity whereas the pharmacophore study also indicates a closer match between the pharmacophore model and the compounds. After comprehensive in silico studies we evolved three best compounds, namely, Vitexin, Isovitexin, and Orientin, which were conducted in vitro assay for further confirmation of their inhibitory activity and results exhibited all of these compounds showed strong inhibitory activity against S. aureus. The overall result suggests that these compounds could be used as a natural lead to inhibit the pathogenesis of S. aureus and antibiotic therapy for S. aureus-associated skin cancer in humans as well

Production, optimization, and physicochemical characterization of biodiesel from seed oil of indigenously grown Jatropha curcas

With the growing demand for vegetable oils, alternative non-edible feedstocks like Jatropha curcas seed oil have gained interest for biodiesel production. The study aimed to comprehensively evaluate the physicochemical properties and biodiesel production potential of locally produced J. curcas seeds in Pakistan. Two different approaches were applied: a chemical synthesis approach involving acidic pretreatment and alkaline transesterification, and a biosynthetic approach using a lipase-producing strain of the Bacillus subtilis Q5 strain. The microbial biosynthesized biodiesel was further optimized using the Plackett–Burman design. The physicochemical properties of the J. curcas methyl esters were analyzed to assess their suitability as biodiesel fuel. Initially, the raw oil had a high free fatty acid content of 13.11%, which was significantly reduced to 1.2% using sulfuric acid pretreatment, keeping the oil to methanol molar ratio to be 1:12. Afterward, alkaline transesterification of purified acid-pretreated seed oil resulted in 96% biodiesel yield at an oil to methanol molar ratio of 1:6, agitation of 600 revolutions per minute (RPM), temperature 60°C, and time 2 h. Moreover, alkaline transesterification yielded ∼98% biodiesel at the following optimized conditions: oil to methanol molar ratio 1:6, KOH 1%, time 90 min, and temperature 60°C. Similarly, the Bacillus subtilis Q5 strain yielded ∼98% biodiesel at the following optimized conditions: oil: methanol ratio of 1:9, agitation 150 RPM, inoculum size 10%, temperature 37°C, and n-hexane 10%. The fuel properties of J. curcas seed biodiesel are closely related to standard values specified by the American Society for Testing and Materials (ASTM D6751–20a), indicating its potential as a viable biodiesel fuel source

Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy

Severe acute respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the etiological virus of Coronavirus Disease 2019 (COVID-19) which has been a public health concern due to its high morbidity and high mortality. Hence, the search for drugs that incapacitate the virus via inhibition of vital proteins in its life cycle is ongoing due to the paucity of drugs in clinical use against the virus. Consequently, this study was aimed at evaluating the potentials of natural phenolics against the Main protease (Mpro) and the receptor binding domain (RBD) using molecular modeling techniques including molecular docking, molecular dynamics (MD) simulation, and density functional theory (DFT) calculations. To this end, thirty-five naturally occurring phenolics were identified and subjected to molecular docking simulation against the proteins. The results showed the compounds including rosmarinic acid, cynarine, and chlorogenic acid among many others possessed high binding affinities for both proteins as evident from their docking scores, with some possessing lower docking scores compared to the standard compound (Remdesivir). Further subjection of the hit compounds to drug-likeness, pharmacokinetics, and toxicity profiling revealed chlorogenic acid, rosmarinic acid, and chicoric acid as the compounds with desirable profiles and toxicity properties, while the study of their electronic properties via density functional theory calculations revealed rosmarinic acid as the most reactive and least stable among the sets of lead compounds that were identified in the study. Molecular dynamics simulation of the complexes formed after docking revealed the stability of the complexes. Ultimately, further experimental procedures are needed to validate the findings of this study

A virtual insight into mushroom secondary metabolites: 3D-QSAR, docking, pharmacophore-based analysis and molecular modeling to analyze their anti-breast cancer potential

Breast cancer is a major issue of investigation in drug discovery due to its rising frequency and global dominance. Plants are significant natural sources for the development of novel medications and therapies. Medicinal mushrooms have many biological response modifiers and are used for the treatment of many physical illnesses. In this research, a database of 89 macro-molecules with anti-breast cancer activity, which were previously isolated from the mushrooms in literature, has been selected for the three-dimensional quantitative structure–activity relationships (3D-QSAR) studies. The 3D-QSAR model was necessarily used in Pharmacopoeia virtual evaluation of the database to develop novel MCF-7 inhibitors. With the known potential targets of breast cancer, the docking studies were achieved. Using molecular dynamics simulations, the targets’ stability with the best-chosen natural product molecule was found. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity of three compounds, resulting after the docking study, were predicted. The compound C1 (Pseudonocardian A) showed the features of effective compounds because it has bioavailability from different coral species and is toxicity-free for the prevention of many dermatological illnesses. C1 is chemically active and possesses charge transfer inside the monomer, as seen by the band gaps of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) electrons. The reactivity descriptors ionization potential, electron affinity, chemical potential (μ), hardness (η), softness (S), electronegativity (χ), and electrophilicity index (ω) have been estimated using the energies of frontier molecular orbitals (HOMO–LUMO). Additionally, molecular electrostatic potential maps were created to show that the C1 is reactive. Communicated by Ramaswamy H. Sarma

Exploring Citrus sinensis Phytochemicals as Potential Inhibitors for Breast Cancer Genes BRCA1 and BRCA2 Using Pharmacophore Modeling, Molecular Docking, MD Simulations, and DFT Analysis

Background: Structure-activity relationship (SAR) is considered to be an effective in silico approach when discovering potential antagonists for breast cancer due to gene mutation. Major challenges are faced by conventional SAR in predicting novel antagonists due to the discovery of diverse antagonistic compounds. Methodologyand Results: In predicting breast cancer antagonists, a multistep screening of phytochemicals isolated from the seeds of the Citrus sinensis plant was applied using feasible complementary methodologies. A three-dimensional quantitative structure-activity relationship (3D-QSAR) model was developed through the Flare project, in which conformational analysis, pharmacophore generation, and compound alignment were done. Ten hit compounds were obtained through the development of the 3D-QSAR model. For exploring the mechanism of action of active compounds against cocrystal inhibitors, molecular docking analysis was done through Molegro software (MVD) to identify lead compounds. Three new proteins, namely, 1T15, 3EU7, and 1T29, displayed the best Moldock scores. The quality of the docking study was assessed by a molecular dynamics simulation. Based on binding affinities to the receptor in the docking studies, three lead compounds (stigmasterol P8, epoxybergamottin P28, and nobiletin P29) were obtained, and they passed through absorption, distribution, metabolism, and excretion (ADME) studies via the SwissADME online service, which proved that P28 and P29 were the most active allosteric inhibitors with the lowest toxicity level against breast cancer. Then, density functional theory (DFT) studies were performed to measure the active compound’s reactivity, hardness, and softness with the help of Gaussian 09 software. Conclusions: This multistep screening of phytochemicals revealed high-reliability antagonists of breast cancer by 3D-QSAR using flare, docking analysis, and DFT studies. The present study helps in providing a proper guideline for the development of novel inhibitors of BRCA1 and BRCA2