Insulin-like antigen of mangrove leaves and its anti-diabetic activity in alloxan-induced diabetic rats

The objective of this study was to evaluate the anti-diabetic potential of three mangrove plants, Rhizophora mucronata, Rhizophora apiculata and Rhizophora annamalayana, and to detect the presence of their insulin-like protein. The in?vivo anti-diabetic experiment was done on male albino Wister rats. Oral administration of 60?mg?kg(-1) leaf powder extract of the three different mangrove plants for 30 days modulated the parameters such as blood glucose, plasma insulin, body weight, total haemoglobin, glycosylated haemoglobin, liver glycogen, plasma and tissue lipids, cholesterol, triglycerides, free fatty acids and phospholipids to normal levels in the alloxan-induced diabetic rats. The anti-diabetic activity of R.?apiculata was more pronounced than that of the other mangrove extracts, but it was on a par with the commercial drug glibenclamide. The presence of an insulin-like protein in the mangrove extracts was detected by SDS-PAGE analysis and confirmed through ELISA. Hence, the anti-diabetic activity and the presence of an insulin-like protein in Rhizophora species were proved scientifically.     

Viologen-based benzylic dendrimers: selective synthesis of 3,5-bis(hydroxymethyl)benzylbromide and conformational analysis of the corresponding viologen dendrimer subunit

Convergent and divergent strategies for the synthesis of viologen dendrimers with 1,3,5-tri-methylene-branching units are discussed. The title compound is easily transformed into 1-[3,5-bis(hydroxymethyl)benzyl]-4-(pyridin-4-yl)pyridinium hexafluorophosphate, which is used in sequential growth and activation steps as a CB₂ compound in the cascade-type dendrimer synthesis (B = -OH, activation = -OH → Br). Analysis of the dendrimer structure reveals that three torsional angles, that is, τ₁ between the two pyridinium units, τ₂ between the methylene and pyridinium and τ₃ between the methylene and phenyl, determine the conformational space of the dendrimers. We report here the crystal structure of 1-[3,5-bis(hydroxymethyl)benzyl]-4-(pyridin-4-yl)pyridinium as PF₆⁻ salt which represents the smallest subunit of the dendrimer that shows the same three torsional angles. The crystal structure together with the results from PM3 calculations opens an avenue to judge the structure of benzylic viologen-based dendrimers.     

Biological evaluation of redox stable cisplatin/Cu(II)-DNA adducts as potential anticancer agents

A series of non-enolizable β-diketonate-based copper(II) complexes with LCuCl₂ [L = Knoevenagel condensates of curcumin (Salcimine) and methylacetoacetate (SalMaA)-based Schiff bases] chromospheres as functional models of chemotherapy drug cisplatin were investigated for their covalent interaction with herring sperm DNA. The synthesis and structural characterization of 1a and 1b have been reported in our previous article. However, their DNA interactions and cytotoxicity properties were not studied. These analyses have been carried out mainly through electrochemical techniques supplemented with spectral, relative viscosity, gel electrophoresis techniques, and AGS cancer cells using MTT assay. The cytotoxic activities of the ligand, curcumin-based copper complex, and cisplatin were tested against the AGS cancer cell line under similar experimental conditions showing that the complex exhibited cancer cell inhibitory rate closer to cisplatin even at low concentration. This was also seen in the docking of the Cu-complex onto a rich guanine B-DNA decamer, where a Cu–N3_(guanine) interaction instead of Pt-N7 as cisplatin is detected. The obtained results in this study prove that these complexes could be a promising substitute for cisplatin as a new family of non-platinum-based anticancer metallo-drugs after in vivo tests on animal models.     

Synthesis and host–guest complexation,photophysical and electrochemical studies on novel thiophenophanes

Synthesis of thiophene-based cyclophanes called thiophenophanes is described. The photophysical and electrochemical properties of thiophenophanes synthesised reveal that they show permanent fluorescence-sensing property, and the cyclic voltammogram reflects the ease with which the electron on the sulphur atom can be removed. Complexation studies of the thiophenophanes with TCNQ reveal the formation of 1:1 complex.     

Synthesis and Photophysical Studies of S-(−)-1,1′-Binaphthol-Based Pyrene-Terminated Dendrimers

Abstract

Pyrene-terminated dendrimers with esters as branching points have been constructed from S-(?)-1,1′-binaphthol as the central core unit utilizing carbodiimide coupling. The chiro-optical properties of the dendrimers reveal that the specific rotation decreases from original to first generation. The photophysical properties of the dendrimers synthesized shows monomeric emission.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Polarographic determination of iron(II) and iron(III) complexes with edta

The iron(II) and iron(III) complexes with EDTA can be determined separately and in mixtures in acetate-buffered medium at pH 4.0. The E_{$\text{1}\text{2}$}values are in the range ?0.105 to ?0.112 V vs. SCE. Linear calibration plots are obtained over the range 0–1.0 mM for each oxidation state. A sample-handling procedure for avoiding oxidation of iron(II) species is described. It is shown that the acetate buffer system does not affect the stability of the iron-EDTA complexes.     

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.     

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.     

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.     

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.