Bioactive Research Articles

A comprehensive review on the development of chiral Cu, Ni, and Zn complexes as pharmaceutical agents over the past decades: Synthesis, molecular structure and biological activity.

Chirality is a fundamental and widespread geometric structural property in living organisms that most biomacromolecules including nucleic acids, proteins and enzymes, possess. Consequently, the development of chiral drugs capable of binding specific targets have gradually gained wide attention in recent decades due to their selective effects on a broad spectrum of biological events ranging from cell metabolism to cell fate. In this context, the synthesis of chiral compounds as promising therapeutic candidates has assumed a major role in drug discovery. Among them, chiral metal complexes have attracted considerable interest due to their unique and intriguing structural features that could enable overcoming side effects and drug-resistance phenomena of metal-based drugs currently in the market such as cisplatin. In the current scenario, an in-depth overview of non-platinum chiral complexes needs to be presented and carried forward. Therefore, in this perspective article, an update of the scientific development of bioactive chiral copper, zinc and nickel complexes have been reported since they have not been thoroughly reviewed so far. Specifically, we focused the article mainly on metal complexes containing chiral ligands (type 2 chirality) as in literature they are more numerous than those with chirality at the metal center (type 1 chirality). Herein, not only their biological activity but also their mechanism of action is summarized. Furthermore, in the final section of the article we have highlighted copper-based complexes as those with a superior biological activity profile and greater prospects for development as a drug.

Microbial Fermentation and Therapeutic Potential of p-Cymene: Insights into Biosynthesis and Antimicrobial Bioactivity

p-Cymene (p-C) [1-methyl-4-(1-methylethyl)-benzene] is a monoterpene found in a variety of plants and has several biological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer properties. This paper explores the microbial fermentation pathways involved in the biosynthesis of p-C, with an emphasis on its potential as a therapeutic agent. Through microbial and biochemical processes, p-C can be produced using renewable precursors such as limonene and 1,8-cineole. Recent advances in fermentation technology have enhanced the efficiency of p-C production, highlighting its role in various industries. Additionally, this paper reviews the antimicrobial bioactivity of p-C, focusing on its ability to inhibit pathogens and modulate immune responses. The integration of microbial biosynthesis and fermentation methods offers a sustainable approach to producing p-C for applications in the perfume, cosmetics, food, and pharmaceutical sectors. Understanding these biosynthetic pathways is crucial for advancing the use of p-C as a bio-based chemical with therapeutic potential. In particular, p-C inhibits the expression of cytokine signal 3 in intestinal inflammation and modulates antioxidant and immunomodulatory systems to protect barrier cells and maintain the mucus layer.

Study on the anti-HBV activity of matrine alkaloids from Oxytropis ochrocephala by MTT, 3d-QSAR, molecular docking and molecular dynamics simulation.

To elucidate the structure-activity relationship of 17 matrine alkaloids from Oxytropis ochrocephala Bunge, their effect on hepatitis B surface antigen (HBsAg) secretion was studied using the MTT assay. A 3D-QSAR analysis showed a strong correlation between chemical structures and biological activities (q2 = 0.625, r2 = 0.859). Molecular docking and molecular dynamics simulations revealed that hydrogen bonding and hydrophobic interactions with hepatitis B core protein (PDB:5T2P) are key to inhibiting HBsAg secretion, suggesting potential for developing natural anti-hepatitis B drugs.

Salt-bridge mediated conformational dynamics in the figure-of-eight knotted ketol acid reductoisomerase (KARI).

The utility of knotted proteins in biological activities has been ambiguous since their discovery. From their evolutionary significance to their functionality in stabilizing the native protein structure, a unilateral conclusion hasn't been achieved yet. While most studies have been performed to understand the stabilizing effect of the knotted fold on the protein chain, more ideas are yet to emerge regarding the interactions in stabilizing the knot. Using classical molecular dynamics (MD) simulations, we have explored the dynamics of the figure-of-eight knotted domain present in ketol acid reductoisomerase (KARI). Our main focus was on the presence of a salt bridge network evident within the knotted region and its role in shaping the conformational dynamics of the knotted chain. Through the potential of mean forces (PMFs) calculation, we have also marked the specific salt bridges that are pivotal in stabilizing the knotted structure. The correlated motions have been further monitored with the help of principal component analysis (PCA) and dynamic cross-correlation maps (DCCM). Furthermore, mutation of the specific salt bridges led to a change in their conformational stability, vindicating their importance.

Antioxidants from Rubus idaeus leaves: LC-MS/MS chemical profiling, in vitro antiglycation, α-glucosidase and α-amylase inhibitory activities

ABSTRACT The present study evaluated a range of biological activities of Rubus idaeus leaves, often considered as by-products, in relation to hyperglycemia. The antiglycation potential of this plant has not been previously reported. In this research, the methanolic leaf extract of R. idaeus was assessed for its antioxidant, enzyme inhibitory and antiglycation activities. The bioactive compounds present in the extract were screened using LC-MS/MS. Enzyme inhibitory activities were tested on α-glucosidase and α-amylase, and the antiglycation effect was investigated using BSA-fructose model. The methanolic extract showed a high polyphenolic contents (176.26 ± 2.26 mg GAE/g) and important IC50 values for DPPH (34.79 ± 2.40 µg/mL) and ABTS radical scavenging activities (49.75 ± 2.47 µg/mL). In addition, the plant leaf extract significantly inhibited hyperglycemia-related enzymes in a dose-dependent manner and demonstrated a reduction in fluorescent AGEs, fructosamine, and dicarbonyl compounds. Therefore, R. idaeus cv Maravilla could be an effective source of therapeutics for improving the healthcare outcomes of diabetic patients.

Synthesis, Antimicrobial Evaluation, Molecular Docking and Dynamics Simulations of Novel 2,3‐Disubstituted Quinazolin‐4(3H)‐one Derivatives

AbstractThe rise of multidrug‐resistant organisms (MDROs) represents a significant challenge to healthcare, underscoring the need for novel antimicrobial agents. Quinazolinone compounds, noted for their diverse biological activities, particularly at the 2nd and 3rd positions, in conjunction with sulphanilamide and isatin derivatives, present a promising avenue for antibacterial development. This study focuses on the synthesis of novel 2,3‐disubstituted quinazolin‐4(3H)‐one derivatives from Schiff base intermediates GA3A and GA3B. The synthesis involved the reaction of 2‐(substituted phenyl)‐4H‐benzo[d][1,3]‐oxazin‐4‐one with sulphanilamide, and the benzoxazinone intermediates were prepared by reacting anthranilic acid with benzoyl chloride. The antibacterial activities of the Schiff base intermediates and the final Mannich base compounds were evaluated against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa at concentrations of 50 µg/mL and 100 µg/mL using the agar well diffusion method, with Norfloxacin (50 µg/mL) as the reference standard. While all tested compounds exhibited lower antibacterial activity compared to the standard, GA4A1 showed enhanced efficacy against E. coli, achieving the highest docking score of 78.0352 against the E. coli protein (PDB ID: 1KZN). Molecular dynamics simulations revealed that the GA4A1‐E. coli complex stabilized after 40,000 ps, with root mean square deviation (RMSD) values ranging from 2.5 Å to 5 Å and low root mean square fluctuation (RMSF) values between 0.05 Å and 0.2 Å, indicating the stability of the complex. These findings underscore GA4A1’s potential as a potent antimicrobial agent against E. coli.

Methodological advances in formulation and assay of herbal resources-based topical drug delivery systems.

Medicinal plants have been utilized for centuries as a source of healing compounds, which consist of thousands of known bioactive molecules with therapeutic potentials. This article aims to explore and emphasize the significance of medicinal plants and bioactive compounds in the development of topical pharmaceutical formulations. The journey from the extraction of phytochemicals to the development of topical pharmaceutical formulations is described with the aid of scientific evidence selected from PubMed, Google Scholar, ScienceDirect, and Web of Science. Articles published in English during 2018-2023 period were considered and selected randomly. The review discusses the extraction process of medicinal plants, solvent selection, and green synthesis of metal nanoparticles. Subsequently, various biological activities of plant extracts are elaborated especially focusing on antimicrobial, antioxidant, anti-inflammatory, and sun protection activities, along with the corresponding invitro assays commonly employed for the evaluation. The article presents the process of compound isolation through bioactivity-guided fractionation and also the toxicity evaluation of isolated fractions. Finally, the formulation of medicinal plant extracts into topical pharmaceuticals is addressed, emphasizing the stability evaluation procedures necessary for ensuring product quality and efficacy.

Valorization of Grape Pomace: A Review of Phenolic Composition, Bioactivity, and Therapeutic Potential

Vitis vinifera L., commonly known as grapes, is one of the most widely cultivated crops worldwide, with over 80% used for wine production. However, the winemaking process generates substantial residues, including grape pomace (GP), wine lees, and wastewater, which can pose significant environmental and economic challenges. Among these, GP stands out not only as a waste product but also as a rich source of polyphenols—bioactive compounds with recognized antioxidant and anti-inflammatory properties. Recent advancements have expanded the application of GP-derived extracts, particularly in the health and food industries, due to their potent bioactive properties. This review provides a comprehensive overview of the valorization of GP, focusing on its phenolic composition and therapeutic potential. It evokes innovative, environmentally friendly extraction techniques and integrated methods for the chemical analysis of these valuable compounds. Additionally, the health benefits of GP polyphenols are explored, with recent experimental findings examining their metabolism and highlighting the key role of gut microbiota in these processes. These insights contribute to a deeper understanding of the biological activity of GP extracts and underscore their growing significance as a high-added-value product. By illustrating how winemaking by-products can be transformed into natural therapeutic agents, this review emphasizes the importance of sustainable development and eco-friendly waste management practices, significantly contributing to the advancement of a circular economy.

Psidium Exotic and Native Species from Brazil Abolish Depression-like Behavior and Oxidative Stress induced by Corticosterone in Mice.

Depression is a highly prevalent neuropsychiatric disorder worldwide. One currently accepted hypothesis of this pathogenesis is the hypothalamic-pituitary-adrenal axis dysfunction, which involves oxidative stress and brain damage. Therefore, antioxidants, such as phenolic compounds, could be used in depression. In this study, we investigated the antidepressant-like and antioxidant effects of an aqueous extract of the leaves of three species of the genus Psidium, Myrtaceae family, in mice. The exotic Psidium guajava L.and the natives Psidium guineense Sw. and Psidium cattleianum Sabine (10, 1, and 0.1 mg/kg, respectively) and fluoxetine (10 mg/kg) were administered orally (p. o.) once daily for 21 days, with or without corticosterone (20 mg/kg). After behavioral assessments (tail suspension, splash, and open-field tests), the hippocampus, prefrontal cortex, liver, kidneys, and plasma were examined to determine the oxidative stress status. The three extracts and fluoxetine treatment decreased the immobility time and counteracted the oxidative stress induced by corticosterone administration. The phenolic compounds identified as major components of the extracts, quercetin in P. guajava and P. guineense and o-coumaric acid in P. cattleianum, may be involved in the biological activities. Therefore, the aqueous leaf extracts of P. guajava, P. cattleianum, and P. guineense could be potential antidepressants helpful in treating depression and other diseases with elevated nitro-oxidative stress.

The Effect of Maturity Stage on Polyphenolic Composition, Antioxidant and Anti-Tyrosinase Activities of Ficus rubiginosa Desf. ex Vent. Extracts

Ficus spp. are often used as food and in traditional medicine, and their biological activities as anti-inflammatory and diuretic, for wound healing, and as antimicrobial agents have been largely reviewed. The aim of this work was to investigate the polyphenol content and the antioxidant and anti-tyrosinase properties of the extracts from F. rubiginosa, a very poorly explored Ficus species. For this purpose, F. rubiginosa leaves were collected at three different maturity stages (H1, H2, and H3), and the environmentally sustainable methanolic extracts were evaluated for the total phenolic content (TPC), total flavonoid content (TFC), and total catechins content (TCC). The polyphenolic profile was studied using HPLC-UV/DAD and UHPLC-MS, and the antioxidant activity was determined in vitro using DPPH, FRAP, and ABTS assays. The study showed that the H2 extract had higher TPC and TFC values (113.50 mg GA/g and 43.27 mg QE/g, respectively) and significant antioxidant activity. Therefore, the H2 extract was selected to study the anti-tyrosinase activity. The results also showed that H2 was able to bind and inhibit tyrosinase, with rutin being the compound responsible for the measured activity on the enzyme.

New Entries in Organocatalysts from an Alkaloid Library; Development of Aminal Catalysis for a Michael Reaction Based on Calycanthine.

Natural products have historically been actively evaluated for their biological activity in the development of pharmaceuticals, while their evaluation as asymmetric catalysts has rarely been explored. In this study, we evaluated the catalytic activity of the natural product library. Three naturally occurring alkaloids, gardnerine, spiradine A, and calycanthine, were found to catalyze an asymmetric Michael reaction using oxindole and nitrostyrene. We further studied (+)-calycanthine, which is characterized by its aminal structure. Concise synthetic and extraction protocols were developed to provide both enantiomers of calycanthine. Further derivatization of this alkaloid led to improved enantioselectivity in a model reaction. Computational studies suggested that the aminal moiety of the catalyst activated nucleophiles and electrophiles through multiple hydrogen bonding interactions, including nonclassical hydrogen bonds between carboxylic acid and the aminal C-H.

Molecular farming expression of recombinant fusion proteins applied to skincare strategies

This review discusses the current research progress in molecular farming technology in the field of skincare, with an emphasis on molecular farming expression strategies. The strategies of transdermal drug delivery and their advantages are also highlighted. The expression of cosmetically relevant fused proteins has become an important way to enhance the efficacy of the proteins. Therefore, we also discuss the feasibility and strategies for expressing fusion proteins in A. thaliana, specifically the fusion of Epidermal growth factor (EGF) to a cell-penetrating peptide (CPP), in which the production can be greatly enhanced via plant expression systems since these systems offer higher biosecurity, flexibility, and expansibility than prokaryotic, animal and mammalian expression systems. While the fusion of EGF to CCP can enhance its transdermal ability, the effects of the fusion protein on skin repair, melasma, whitening, and anti-aging are poorly explored. Beyond this, fusing proteins with transdermal peptides presents multiple possibilities for the development of tissue repair and regeneration therapeutics, as well as cosmetics and beauty products. As certain plant extracts are known to contain proteins beneficial for skin health, the expression of these proteins in plant systems will better maintain their integrity and biological activities, thereby facilitating the development of more effective skincare products.

Efficient removal of organic matter and nitrogen from municipal wastewater in multi-module biochar filters for onsite wastewater treatment

ABSTRACT Biochar is a promising material for wastewater treatment. This study assessed multi-module biochar filters (MmBFs) as onsite wastewater treatment systems (OWTSs), comprising movable modules filled with biochar to remove chemical oxygen demand (COD), nitrogen, phosphorus, and Escherichia coli (E. coli) in wastewater. The MmBF treats wastewater sequentially through six modules: three aerobic modules (M1-M3) for organic matter oxidation and nitrification, two anoxic modules (M4-M5) for denitrification, and an additional module (M6) for the removal of faecal bacteria using biochar and bark. The experiments ran for 381 days using three identical MmBF pilots with two distinct sampling periods, conducted under conditions relevant to OWTSs using municipal wastewater as influent. Water samples were taken from the influent, final effluent, and effluent of each module to evaluate the removal efficiency of organic matter, nitrogen, phosphorus, and E. coli. During the second sampling period, the results showed a 95 ± 2.1% removal of COD, along with a substantial removal of total inorganic nitrogen (71 ± 6.6%). However, phosphate removal was limited (3.4 ± 30.4%). E. coli removal decreased from 2.63 ± 0.93 log10 removal in the first sampling period to 1.8 ± 0.73 log10 removal in the second sampling period. In summary, the MmBFs showed promising potential in treating organic matter, nitrogen, and E. coli, making it an alternative option for OWTS. However, further exploration is needed to assess long-term performance, micropollutant removal, and biological activities. Design enhancements, especially for phosphorus removal are necessary.

Transcriptomic Analysis Reveals Diverse Expression of Scorpion Toxin Genes in Mesobuthus martensii

Scorpions, an ancient group of venomous invertebrates, have existed for over 430 million years. Their toxins, important for predation and defense, exhibit a variety of biological and pharmacological activities. Research on scorpion toxins has spanned decades. Notably, the toxin genes of Mesobuthus martensii (Scorpiones: Buthidae), a well-known Chinese herbal medicine, have been described at genomic and proteomic levels. However, previous studies primarily focused on the toxin genes expressed in the venom glands, overlooking their expression in multiple tissues. This study analyzed transcriptomes from 14 tissues of M. martensii. Gene annotation revealed 83 toxin and toxin-like genes, including those affecting sodium, potassium, calcium, and chloride ion channels. Approximately 70% of toxin genes were highly expressed in the vesicle; additionally, some exhibited low or no expression in the vesicle while showing high expression in other tissues. Beyond the vesicle, high expression levels of toxin genes were observed in metasoma segments II-V, blood, lateral eyes, chelicerae, legs, pedipalp chelae, femurs, and patellae. This expression pattern suggests that toxin genes are recruited from multiple tissues and may help prevent intraspecific harm during courtship and competition for prey. These findings inspire further research into the evolutionary recruitment process of scorpion toxins.

Design, Synthesis, and Antimicrobial Evaluation of Novel Schiff Bases Derived from Thymol

Schiff bases, a significant class of organic compounds, are synthesized through the reaction of a primary amine with an aldehyde or ketone under specific conditions. In this study, we report the synthesis of novel Schiff bases derived from thymol (2-Isopropyl-5-methylphenol). The synthesis began with the esterification of thymol to produce (2-Isopropyl-5-methylphenoxy)-acetic acid ethyl ester (1), followed by hydrazination to yield (2-Isopropyl-5-methylphenoxy)-acetic acid hydrazide (2). The hydrazide (2) was then treated with various aromatic aldehydes to synthesize a series of Schiff bases (3A-J). The chemical structures of these compounds were elucidated using infrared (IR) spectroscopy, proton nuclear magnetic resonance (1H-NMR), and mass spectrometry. The synthesized Schiff bases were evaluated for their antibacterial and antifungal activities using standard screening methods. The results indicated that all synthesized compounds exhibited varying degrees of antimicrobial activity. Among the series, compound 3C showed the highest antibacterial and antifungal potency, suggesting it could be a promising candidate for further development. This study highlights the potential of Schiff bases as bioactive compounds with broad-spectrum antimicrobial properties. The structure-activity relationship (SAR) suggests that the presence of specific substituents on the aromatic aldehyde moiety could enhance biological activity. Further investigation into the mechanisms of action and optimization of these Schiff bases could contribute to the development of novel antimicrobial agents

Eco-friendly synthesis and characterization of ZnO and Mg-Ag-doped ZnO nanoparticles using Phoenix dactylifera L. seeds: exploring biological activity and structural properties

Eco-friendly synthesis and characterization of ZnO and Mg-Ag-doped ZnO nanoparticles using Phoenix dactylifera L. seeds: exploring biological activity and structural properties

In silico Study with Antioxidant Activity and α-Amylase Inhibitory Potential in Ethanolic Extract of Melilotus indicus

Building upon the long history of plants as natural remedies, this study investigated the presence and content of flavonoids, a class of polyphenols, in an ethanolic extract of Melilotus indicus. The antioxidant activity of the extract was also evaluated. The Melilotus genus is renowned for its diverse biological activities, including antioxidant, anti-inflammatory, and hypoglycemic effects. As anticipated, flavonoids were the primary phenolic constituents identified in M. indicus. The extract exhibited a flavonoid content of 0.49 ± 3.818 mg/g and demonstrated comparable antioxidant activity (IC50 = 1.6 mg/mL) to vitamin C (IC50 = 0.01 mg/mL). A docking study against human salivary amylase (1C8Q), revealed promising binding scores for chlorogenic acid and kaempferol (-6.09196091 and -5.45953274 kcal/mol, respectively) compared to the acarbose drug (-8.8864727 kcal/mol). These findings suggest that M. indicus may be a valuable source of natural antioxidants with potential health benefits.

Recent advancement of novel marine fungi derived secondary metabolite fibrinolytic compound FGFC in biomedical applications: a review

For several decades, products derived from marine natural sources (PMN) have been widely identified for several therapeutic applications due to their rich sources of bioactive sub-stances, unique chemical diversity, biocompatibility and excellent biological activity. For the past 15 years, our research team explored several PMNs, especially fungi fibrinolytic compounds (FGFCs). FGFC is an isoindolone alkaloid derived from marine fungi, also known as staplabin analogs or Stachybotrys microspora triprenyl phenol (SMTP). For instance, our previous studies explored different types of FGFCs such as FGFC 1, 2, 3 and 4 from the marine fungi Stachybotrys longispora FG216 derived metabolites. The derivatives of FGFC are potentially employed in several disease treatments, mainly for stroke, cancer, ischemia, acute kidney injury, inflammation, cerebral infarction, thrombolysis and hemorrhagic activities, etc. Due to the increasing use of FGFCs in pharmaceutical and biomedical applications, it is important to understand the fundamental signaling concept of FGFCs. Hence, for the first time, this review collectively summarizes the background, types, mode of action and biological applications of FGFCs and their current endeavors for future therapies.

New Insights Into The Antibacterial Activity Of Hydroxytyrosol Extracted From Olive Leaves: Molecular Docking Simulations Of Its Antibacterial Mechanisms.

This study investigated the biological activities of a hydroxytyrosol-rich extract from Oleaeuropaea leaves, particularly its ability to eradicate severe pathogenic bacteria producing Extended-Spectrum Beta-Lactamases (ESBLs). The latter bacteria are emerging microorganisms that pose significant challenges due to their resistance to a broad range of potent therapeutic drugs. The extract was prepared through an accessible acid hydrolysis method. In vitro and In silico analyses through MIC, MBC analysis and molecular docking were conducted to evaluate the antibacterial properties. The extract showed remarkable antioxidant activity and significant antibacterial potential against reference species and ESBL bacteria. MIC and MBC calculations confirmed the extract's capacity to kill bacteria rather than just inhibit their growth. Further in silico analyzes demonstrated the high binding affinity of HT to the active sites of the gyrase B subunit and the peptidoglycan DD-transpeptidase domain from proteins located in the cytoplasm and the cell wall of the bacteria, respectively. Results confirmed the structure-activity relationship and the ability of HT to disrupt essential bacterial functions. This study validates the debated antimicrobial potential of HT and highlights its importance as a potential therapeutic agent against resistant bacteria, which is a critical area of research given the global challenge of antibiotic resistance.

Metal-organic frameworks (MOFs) and their derivatives as emerging biomaterials for the treatment of osteoarthritis

As a novel class of smart biomaterials with promising potentials, metal-organic frameworks (MOFs) are widely utilized in the field of biomedicine. Current researches indicate that the therapeutic strategies for osteoarthritis (OA) are highly limited to achieving symptom improvement and reducing both pain and inflammation. Together, the introduction of MOFs into the treatment of OA holds the potential to offer significant benefits. This is because MOFs not only have intrinsic biological activities, but also act as carriers to facilitate controlled drug delivery and prolong the duration in the management of OA. This paper presents a review of the recent studies that have explored the potential usage of MOFs as drugs or carriers in the treatment of OA, which also examines the progress of MOFs in tissue engineering for the treatment of OA. These studies are anticipated to not only enhance the comprehension of MOFs but also provide strong evidence in favor of their utilization in the treatment of OA.