Ameliorative Role of Nutraceutical Quercetin and its Derivatives Against Cognitive Impairment Process Induced by Lead Exposure in Drosophila melanogaster(Fruit Fly)

Cumulative lifetime lead (Pb) exposure has been associated with accelerated declines in cognition through the free radical generation and epigenetic effects. Several pieces of literature have identified a correlation between exposure to lead and neurodegenerative disorders. Harwich strain Drosophila melanogaster was exposed to lead acetate for two weeks, and changes in pulse transmission by acetylcholinesterase and systemic redox were evaluated. Besides, molecular docking studies of acetylcholinesterase against Quercetin and its most common derivatives contained in food have been performed. Pharmacokinetic studies on Quercetin and its derivatives have also been performed in silico toxicity. The data obtained showed alterations in antioxidant enzymes and molecules such as catalase, glutathione-S-transferase, and glutathione. Upregulation of acetylcholinesterase activity was observed after treatment with Quercetin. In molecular docking tests, Quercetin and its derivatives were found to bind to acetylcholinesterase's active and peripheral pockets. Pharmacokinetic studies demonstrate moderate solubility, high therapeutic index, excellent absorption potential, hepatoprotective and non-mutagenic properties. With other antioxidant molecules, Quercetin may also play a crucial role in avoiding the development of Alzheimer's and associated antioxidant disorders.

Visible-light driven regioselective synthesis, characterization and binding studies of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines with DNA and BSA using biophysical and computational techniques

In recent times, fused azaheterocycles emerged as impressive therapeutic agents. Binding studies of such azaheterocycles with biomolecules is an important subject for pharmaceutical and biochemical studies aiming at the design and development of new drugs. Fused heterocyclic scaffolds, such as thiazolopyrmidines have long been used in the pharmaceutical industry for the treatment of various diseases. In this study, we have accomplished a regioselective synthesis of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines by the reaction of tetrahydropyrimidine-2(H)-thione with α-bromo-1,3-diketones, generated in situ from 1,3-diketones and NBS, using visible light as an inexpensive, green and renewable energy source under mild reaction conditions with wide-ranging substrate scope. The regioisomer was characterized unambiguously by 2D-NMR [1H-13C] HMBC and [1H-13C] HMQC spectroscopy. In silico toxicity data analysis showed the low toxicity risks of the synthesized compounds. Computational molecular docking studies were carried out to examine the interaction of thiazolo[3,2-a]pyrimidines with calf-thymus DNA (ct-DNA) and Bovine Serum Albumin (BSA). Moreover, different spectroscopic approaches viz. steady-state fluorescence, competitive displacement assay, UV–visible and circular dichroism (CD) along with viscosity measurements were employed to investigate the binding mechanisms of thiazolo[3,2-a]pyrimidines with DNA and BSA. The results thus obtained revealed that thiazolo[3,2-a]pyrimidines offer groove bindings with DNA and showed moderate bindings with BSA.

Isopropyl Ricinoleate, A Potential Alternative to Isopropyl Myristate: Experimental and Computational evaluation

Background: Due to growing environmental concerns, eco-friendly and sustainable materials have become one of the key interests of cosmetics research. Isopropyl myristate is being used as a major cosmetic ingredient, like in many other cosmetic items, as an emollient for a long time. Methods: An emollient ester, isopropyl ricinoleate, is derived from non-edible oil, castor oil. The synthesized isopropyl ricinoleate using greener enzyme catalysed methodology was further tested for sensory evaluation and transepidermal water loss (TEWL) studies. Results: An ester, isopropyl ricinoleate, imparted better gloss and shine to the skin as compared to isopropyl myristate due to its higher refractive index. Both esters, isopropyl ricinoleate and isopropyl myristate, showed minimum tackiness and residue after spreading. Moreover, in-silico toxicity analysis of ester, isopropyl ricinoleate, supported previously reported in-vitro toxicity data. Conclusion: Thus, the current study provides better insights on the replacement of emollient ester isopropyl myristate by isopropyl ricinoleate.

Characterization and In-silico toxicity prediction of degradation products of felbamate

Background The objective of the work carried out was to assess the toxicity of the degradation products (DPs) for the drug felbamate. Stress studies were performed in the condition specified in the international council of harmonization (ICH) guideline Q1A (R2). Results The drug degraded under the alkaline stress conditions to generate two degradation products (DPs). They were separated on a Phenomenex C8 column (250 mm × 4.6 mm, 5 µm); mobile phase composition was 10 mM ammonium formate (pH adjusted to 3.7 with formic acid) and acetonitrile (80:20, v/v); flow rate and wavelength for recording absorbance were 1.0 ml/min and 206 nm, respectively. The structures of the degradation products were characterized by LC–MS/MS analysis. Conclusion The drug was prone to hydrolysis in the presence of alkali. It was found to be stable under other stress conditions, viz., acidic, neutral, thermal, photolytic and oxidative. The structures of the impurities were characterized by LC–MS/MS. The drug and the DPs were screened through ADME and toxicity prediction software’s like pkCSM, Toxtree and OSIRIS property explorer. Felbamate was flagged for possible hepatotoxicity.

ISOLATION, CHARACTERIZATIONS, ANTI-CANCER, CYTOTOXICITY, IN SILICO TOXICITY, AND ANTIMICROBIAL EVALUATIONS OF MORINGA OLEIFERA SEED PROTEIN

Background: Moringa oleifera seed, which is widely utilized as an affordable source of domestic water treatment, is also reputable for its various pharmacological applications globally. Aim: This study evaluates the toxicity and pharmacological potentials of Moringa oleifera seed protein while establishing the chemical profile. Method: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS/MS) were used to analyze the protein/peptide content of the purified protein. The protein was also investigated for in vitro anticancer potential on Hela and MDA-MB-231 cell lines, cytotoxic on 3T3 cell line, and toxicity to brine shrimps. In addition, the antimicrobial action of the protein (polypeptide) was evaluated. Results and Discussion: The MALDI-MS revealed three protein moieties with values of 3.4, 4.6, and 6.9 kDa. On the other hand, LC-ESIMS/MS analysis revealed dipeptides and tripeptides, which include serinylarginine, leucylproline, leucylmethionyl-glycine, isoleucyl-glycyl-methinine, glycyl-arginyl-aspartic acid, isoleucyl-glutamyl-methionine, diphenylalanine, asparaginyl-aspartyl-histidine, seryl-tyrosyl-tyrosine, phenylalanyl-asparaginyl-tyrosine, and propanolyl-trytophanyl-glycine. The seed protein exhibited extremely low toxicity on both 3T3 and MDA-MB-231 breast cancer cell lines, while the standards, doxorubicin, and cycloheximide had IC50 = 0.5 ± 0.07 and 0.8 ± 0.10 μg/mL, respectively. Further, the protein showed no antibacterial or antifungal activity against all tested organisms. The protein also exhibited no lethality against brine shrimp. The in-silico toxicity results indicated that the peptides are not immunotoxic, carcinogenic, or mutagenic as most belonged to the tox class V except serylarginine predicted for tox class IV (harmful if swallowed). Hence, the intake of the protein remnant in water could be within the tolerable limit. Conclusion: The results obtained suggested that the protein content of the Moringa oleifera seed is non-cytotoxic. The result further validates the safety potential of the defatted and debittered seed material used as potential food sources for both humans and animals.

Composition of the Essential Oil Thymus schimperi and Evaluation of Its Acute and Subacute Toxicity in Wistar Albino Rats: In Silico Toxicity Studies

Background. In Ethiopian traditional medicine, the aerial part of Thymus schimperi is widely used to treat diseases such as gonorrhea, cough, liver disease, kidney disease, hypertension, stomach pain, and fungal skin infections. However, there is insufficient investigation on the toxic effect of the essential oil of T. schimperi. The aim of this study was, therefore, to evaluate the acute, subacute, and in silico toxicity of Thymus schimperi essential oil in the Wistar albino rats. Method. Essential oil of the aerial part of T. schimperi extracted by hydrodistillation was analyzed by GC-MS. The oil was subjected to toxicity studies. In the acute toxicity study, rats were randomly divided into seven groups (n = 5). The control group received only distilled water with 2% of tween 80, whereas the experimental groups received single doses of 300, 600, 900, 1200, 1500, and 2 000 mg/kg of the oil. In the subacute toxicity study, rats were randomly divided into four groups (n = 10). The control group received distilled water with 2% of tween 80, whereas the experimental groups received 65 mg/kg, 130 mg/kg, and 260 mg/kg of the oil orally for 28 days. At the end of the experiment, blood samples were collected for hematology and clinical chemistry evaluation. Gross pathology and histopathology of the liver and the kidneys were also evaluated. For the in silico toxicity study, PubChem CID numbers of GC-MS identified bioactive compounds in the essential oil of T. schimperi obtained from PubChem. Chemdraw (8.0) was used to construct two-dimensional structures of the compounds. The Swiss ADMET web tool was used to convert the two-dimensional structures into a simplified molecular-input line input system (SMILES). In addition, the toxicity parameters were predicted via vNN and ADMET servers. Results. In this study, the LD50 of the essential oil of T. schimperi was found to be 1284.2 mg/kg. According to the World Health Organization, the oil is classified as moderately hazardous in its oral administration. In the subacute toxicity study, rats showed no significant changes in behavioral indices, gross pathology, body weight, biochemical, and most hematological parameters. However, hematological profiles showed a significant decrement in WBC counts and a significant increment of MCV in high dose (260 mg/kg) groups as compared to the control group. Furthermore, no significant differences were observed between the control and essential oil-treated groups, observed in the gross histopathology of the liver and the kidneys. In the in silico toxicity study, all compounds derived from the essential oil showed no cardiac toxicity (h-ERG Blocker), AMES (Ames Mutagenicity), and cytotoxicity via ADMET and vNN-ADMET toxicity predictors. However, by using these servers, about 8.6% of the compounds showed hepatotoxicity, only 3.45% caused drug-induced liver injury, and only 1.75% were potentially toxic to the mitochondrial membrane. Conclusion. From the results of this study, oral administration of the essential oil T. schimperi up to a dose of 130 mg/kg is not harmful. However, in the high-dose (260 mg/kg) group, the WBC count was significantly decreased and the MCV was significantly increased. In the in silico toxicity study, most of the components of the oil were found to be nontoxic, although a few of the compounds showed hepatotoxicity and mitochondrial membrane potential toxicity. It is, therefore, essential to conduct chronic toxicity of the essential oil as well as its components, which showed toxicity in the in silico study before using preparations containing the essential oil of T. schimperi.