Silibinin and Naringenin against Bisphenol A-Induced Neurotoxicity in Zebrafish Model—Potential Flavonoid Molecules for New Drug Design,Development, and Therapy for Neurological Disorders

Bisphenol A (BPA), a well-known xenoestrogen, is commonly utilised in the production of polycarbonate plastics. Based on the existing evidence, BPA is known to induce neurotoxicity and behavioural issues. Flavonoids such as silibinin and naringenin have been shown to have biological activity against a variety of illnesses. The current research evaluates the neuropharmacological effects of silibinin and naringenin in a zebrafish model against neurotoxicity and oxidative stress caused by Bisphenol A. In this study, a novel tank diving test (NTDT) and light–dark preference test (LDPT) were used in neurobehavioural investigations. The experimental protocol was planned to last 21 days. The neuroprotective effects of silibinin (10 μM) and naringenin (10 μM) in zebrafish (Danio rerio) induced by BPA (17.52 μM) were investigated. In the brine shrimp lethality assay, the 50% fatal concentrations (LC₅₀) were 34.10 μg/mL (silibinin) and 91.33 μg/mL (naringenin) compared to the standard potassium dichromate (13.15 μg/mL). The acute toxicity investigation found no mortality or visible abnormalities in the silibinin- and naringenin-treated groups (LC₅₀ > 100 mg/L). The altered scototaxis behaviour in LDPT caused by BPA was reversed by co-supplementation with silibinin and naringenin, as shown by decreases in the number of transitions to the light zone and the duration spent in the light zone. Our findings point to BPA’s neurotoxic potential in causing altered scototaxis and bottom-dwelling behaviour in zebrafish, as well as the usage of silibinin and naringenin as potential neuroprotectants.     

Genistein: A Potential Natural Lead Molecule for New Drug Design and Development for Treating Memory Impairment

Genistein is a naturally occurring polyphenolic molecule in the isoflavones group which is well known for its neuroprotection. In this review, we summarize the efficacy of genistein in attenuating the effects of memory impairment (MI) in animals. Scopus, PubMed, and Web of Science databases were used to find the relevant articles and discuss the effects of genistein in the brain, including its pharmacokinetics, bioavailability, behavioral effects, and some of the potential mechanisms of action on memory in several animal models. The results of the preclinical studies highly suggested that genistein is highly effective in enhancing the cognitive performance of the MI animal models, specifically in the memory domain, including spatial, recognition, retention, and reference memories, through its ability to reduce oxidative stress and attenuate neuroinflammation. This review also highlighted challenges and opportunities to improve the drug delivery of genistein for treating MI. Along with that, the possible structural modifications and derivatives of genistein to improve its physicochemical and drug-likeness properties are also discussed. The outcomes of the review proved that genistein can enhance the cognitive performance and ameliorate MI in different preclinical studies, thus indicating its potential as a natural lead for the design and development of a novel neuroprotective drug.     

Mannich reaction of pyrrole and dimethylpyrrole with monoamines and diamines

The Mannich reaction of pyrrole with ethylenediamine dihydrochloride and formaldehyde gave two compounds: N¹,N¹,N²,N²-tetrakis(pyrrol-2-ylmethyl)ethane-1,2-diamine 1 and 1,3-bis(pyrrol-2-ylmethyl)imidazolidine 2 in poor yields. Conversely, the reaction of pyrrole with propylenediamine dihydrochloride afforded macrocyclic compound 3 containing two pyrrole rings bridged by two dimethylenehexahydropyrimidine moieties in 50% yield. The reaction of 2,5-dimethylpyrrole with methylamine hydrochloride and formaldehyde gave novel bicycle 4 consisting of a dimethyltetrahydro-1,3-diazepine ring fused with a 2,5-dimethylpyrrole ring. The reaction of 2,5-dimethylpyrrole with ammonium chloride gave the tripodal ligand tris(2,5-dimethylpyrrol-3-yl)methylamine 5 in 62% yield. The structures of 2–4 were determined by single crystal X-ray diffraction studies.     

Chemistry,Biosynthesis and Pharmacology of Sarsasapogenin: A Potential Natural Steroid Molecule for New Drug Design,Development and Therapy

Sarsasapogenin is a natural steroidal sapogenin molecule obtained mainly from Anemarrhena asphodeloides Bunge. Among the various phytosteroids present, sarsasapogenin has emerged as a promising molecule due to the fact of its diverse pharmacological activities. In this review, the chemistry, biosynthesis and pharmacological potentials of sarsasapogenin are summarised. Between 1996 and the present, the relevant literature regarding sarsasapogenin was obtained from scientific databases including PubMed, ScienceDirect, Scopus, and Google Scholar. Overall, sarsasapogenin is a potent molecule with anti-inflammatory, anticancer, antidiabetic, anti-osteoclastogenic and neuroprotective activities. It is also a potential molecule in the treatment for precocious puberty. This review also discusses the metabolism, pharmacokinetics and possible structural modifications as well as obstacles and opportunities for sarsasapogenin to become a drug molecule in the near future. More comprehensive preclinical studies, clinical trials, drug delivery, formulations of effective doses in pharmacokinetics studies, evaluation of adverse effects and potential synergistic effects with other drugs need to be thoroughly investigated to make sarsasapogenin a potential molecule for future drug development.     

Antibacterial Potential of Bacopa monnieri (L.) Wettst. and Its Bioactive Molecules against Uropathogens—An In Silico Study to Identify Potential Lead Molecule(s) for the Development of New Drugs to Treat Urinary Tract Infections

Urinary tract infections (UTIs) are becoming more common, requiring extensive protection from antimicrobials. The global expansion of multi-drug resistance uropathogens in the past decade emphasizes the necessity of newer antibiotic treatments and prevention strategies for UTIs. Medicinal plants have wide therapeutic applications in both the prevention and management of many ailments. Bacopa monnieri is a medicinal plant that is found in the warmer and wetlands regions of the world. It has been used in Ayurvedic systems for centuries. The present study aimed to investigate the antibacterial potential of the extract of B. monnieri leaves and its bioactive molecules against UTIs that are caused by Klebsiella pneumoniae and Proteus mirabilis. This in vitro experimental study was conducted by an agar well diffusion method to evaluate the antimicrobial effect of 80% methanol, 96% ethanol, and aqueous extracts of B. monnieri leaves on uropathogens. Then, further screening of their phytochemicals was carried out using standard methods. To validate the bioactive molecules and the microbe interactions, AutoDock Vina software was used for molecular docking with the Klebsiella pneumoniae fosfomycin resistance protein (5WEW) and the Zn-dependent receptor-binding domain of Proteus mirabilis MR/P fimbrial adhesin MrpH (6Y4F). Toxicity prediction and drug likeness were predicted using ProTox-II and Molinspiration, respectively. A molecular dynamics (MD) simulation was carried out to study the protein ligand complexes. The methanolic leaves extract of B. monnieri revealed a 22.3 mm ± 0.6 mm to 25.0 mm ± 0.5 mm inhibition zone, while ethanolic extract seemed to produce 19.3 mm ± 0.8 mm to 23.0 mm ± 0.4 mm inhibition zones against K. pneumoniae with the use of increasing concentrations. In the case of P. mirabilis activity, the methanolic extracts showed a 21.0 mm ± 0.8 mm to 24.0 mm ± 0.6 mm zone of inhibition and the ethanol extract produced a 17.0 mm ± 0.9 mm to 23.0 mm ± 0.7 mm inhibition zone with increasing concentrations. Carbohydrates, flavonoids, saponin, phenolic, and terpenoid were common phytoconstituents identified in B. monnieri extracts. Oroxindin showed the best interactions with the binding energies with 5WEW and 6Y4F, −7.5 kcal/mol and −7.4 kcal/mol, respectively. Oroxindin, a bioactive molecule, followed Lipinski’s rule of five and exhibited stability in the MD simulation. The overall results suggest that Oroxindin from B. monnieri can be a potent inhibitor for the effective killing of K. pneumoniae and P. mirabilis. Additionally, its safety has been established, indicating its potential for future drug discovery and development in the treatment for UTIs.     

Sulfonium cations as versatile strongly π-acidic ligands

More than a century old, sulfonium cations are still intriguing species in the landscape of organic chemistry. On one hand they have found broad applications in organic synthesis and materials science, but on the other hand, while isoelectronic to the ubiquitous tertiary phosphine ligands, their own coordination chemistry has been neglected for the last three decades. Here we report the synthesis and full characterization of the first Rh(i) and Pt(ii) complexes of sulfonium. Moreover, for the first time, coordination of an aromatic sulfonium has been established. A thorough computational analysis of the exceptionally short S–Rh bonds obtained attests to the strongly π-accepting nature of sulfonium cations and places them among the best π-acceptor ligands available today. Our calculations also show that embedding within a pincer framework enhances their π-acidity even further. Therefore, in addition to the stability and modularity that these frameworks offer, our pincer complexes might open the way for sulfonium cations to become powerful tools in π-acid catalysis.

Back to the scene: while isolobal to the ubiquitous tertiary phosphines, sulfonium cations as ligands were neglected for decades. This work revives the coordination chemistry of these species showing their potential as ligands for π-acid catalysis.     

Isolation,Purification and Characterisation of Low Molecular Weight Xylanase from <Emphasis Type="Italic">Bacillus pumilus</Emphasis> SSP-34

Low molecular weight endo-xylanase from Bacillus pumilus SSP-34 was purified to homogeneity using ion exchange and size exclusion chromatographies. Xylanases were isolated by novel purification protocol which includes the use of anion exchange matrix such as DEAE Sepharose CL 6B with less affinity towards enzyme protein. The purified B. pumilus SSP-34 have a molecular weight of 20 kDa, with optimum pH and temperature at 6.0 and 50 °C, respectively. The enzyme was stable at 50 °C for 30 min. It showed remarkable stability at pH values ranging from 4.5 to 9 when the reaction was carried out at 50 °C. K _m and V _max values, determined with oats spelts xylan were 6.5 mg ml⁻¹ and 1,233 μmol min⁻¹ mg⁻¹ protein, respectively, and the specific activity was 1,723 U mg⁻¹     

Synthesis of trans‐Disubstituted Alkenes by Cobalt‐Catalyzed Reductive Coupling of Terminal Alkynes with Activated Alkenes

A cobalt‐catalyzed reductive coupling of terminal alkynes, RC?CH, with activated alkenes, R′CH?CH₂, in the presence of zinc and water to give functionalized trans‐disubstituted alkenes, RCH?CHCH₂CH₂R′, is described. A variety of aromatic terminal alkynes underwent reductive coupling with activated alkenes including enones, acrylates, acrylonitrile, and vinyl sulfones in the presence of a CoCl₂/P(OMe)₃/Zn catalyst system to afford 1,2‐trans‐disubstituted alkenes with high regio‐ and stereoselectivity. Similarly, aliphatic terminal alkynes also efficiently participated in the coupling reaction with acrylates, enones, and vinyl sulfone, in the presence of the CoCl₂/P(OPh)₃/Zn system providing a mixture of 1,2‐trans‐ and 1,1‐disubstituted functionalized terminal alkene products in high yields. The scope of the reaction was also extended by the coupling of 1,3‐enynes and acetylene gas with alkenes. Furthermore, a phosphine‐free cobalt‐catalyzed reductive coupling of terminal alkynes with enones, affording 1,2‐trans‐disubstituted alkenes as the major products in a high regioisomeric ratio, is demonstrated. In the reactions, less expensive and air‐stable cobalt complexes, a mild reducing agent (Zn) and a simple hydrogen source (water) were used. A possible reaction mechanism involving a cobaltacyclopentene as the key intermediate is proposed.     

Computational Approach for Identification of Anopheles gambiae miRNA Involved in Modulation of Host Immune Response

MicroRNAs (miRNAs) are small, noncoding RNAs that play key roles in regulating gene expression in animals, plants, and viruses, which involves in biological processes including development, cancer, immunity, and host–microorganism interactions. In this present study, we have used the computational approach to identify potent miRNAs involved in Anopheles gambiae immune response. Analysis of 217,261 A. gambiae ESTs and further study of RNA folding revealed six new miRNAs. The minimum free energy of the predicted miRNAs ranged from ?27.2 to ?62.63 kcal/mol with an average of ?49.38 kcal/mol. While its A + U % ranges from 50 to 65 % with an average value of 57.37 %. Phylogenetic analysis of the predicted miRNAs revealed that aga-miR-277 was evolutionary highly conserved with more similarity with other mosquito species. Observing further the target identification of the predicted miRNA, it was noticed that the aga-miR-2304 and aga-miR-2390 are involved in modulation of immune response by targeting the gene encoding suppressin and protein prophenoloxidase. Further detailed studies of these miRNAs will help in revealing its function in modulation of A. gambiae immune response with respect to its parasite.