Heterocyclic Substitutions Greatly Improve Affinity and Stability of Folic Acid towards FRα. an In Silico Insight

Folate receptor alpha (FRα) is known as a biological marker for many cancers due to its overexpression in cancerous epithelial tissue. The folic acid (FA) binding affinity to the FRα active site provides a basis for designing more specific targets for FRα. Heterocyclic rings have been shown to interact with many receptors and are important to the metabolism and biological processes within the body. Nineteen FA analogs with substitution with various heterocyclic rings were designed to have higher affinity toward FRα. Molecular docking was used to study the binding affinity of designed analogs compared to FA, methotrexate (MTX), and pemetrexed (PTX). Out of 19 FA analogs, analogs with a tetrazole ring (FOL03) and benzothiophene ring (FOL08) showed the most negative binding energy and were able to interact with ASP81 and SER174 through hydrogen bonds and hydrophobic interactions with amino acids of the active site. Hence, 100 ns molecular dynamics (MD) simulations were carried out for FOL03, FOL08 compared to FA, MTX, and PTX. The root mean square deviation (RMSD) and root mean square fluctuation (RMSF) of FOL03 and FOL08 showed an apparent convergence similar to that of FA, and both of them entered the binding pocket (active site) from the pteridine part, while the glutamic part was stuck at the FRα pocket entrance during the MD simulations. Molecular mechanics Poisson-Boltzmann surface accessible (MM-PBSA) and H-bond analysis revealed that FOL03 and FOL08 created more negative free binding and electrostatic energy compared to FA and PTX, and both formed stronger H-bond interactions with ASP81 than FA with excellent H-bond profiles that led them to become bound tightly in the pocket. In addition, pocket volume calculations showed that the volumes of active site for FOL03 and FOL08 inside the FRα pocket were smaller than the FA–FRα system, indicating strong interactions between the protein active site residues with these new FA analogs compared to FA during the MD simulations.     

Electronic structures of carbazole and its derivatives: A semi-empirical study on the substitution effects of carbazole

The electronic structures of carbazole, N-phenylcarbazole (NPC), cyanophenylcarbazole (CPC) and N-ethylcarbazole (NEC) have been calculated using the quantum chemical semi-empirical MINDO/3 method. In this paper, electronic ground states and first singlet excited states of the systems mentioned were investigated. It is observed that the excitation energy of carbazole based on the calculated difference in heats of formation agrees quite well with experimental data obtained from supersonic expansion studies. Calculated energy levels of molecular orbitals and their graphical forms are used qualitatively in elucidating the S₀ → S₁ excitation electronic origin red shifts observed in carbazole derivatives with respect to the electronic origin of the parent carbazole. It is noted that the red shifts are not just a result of the destabilization of the HOMO of carbazole but are also determined by the nature of the substituting moieties. It is also observed that the LUMO of CPC is not derived from the parent carbazole which partially explains the difference in electronic behaviour as compared with the other derivatives.     

Development and Characterization of Novel Biopolymer Derived from Abelmoschus esculentus L. Extract and Its Antidiabetic Potential

Abelmoschus esculentus (Okra) is an important vegetable crop, widely cultivated around the world due to its high nutritional significance along with several health benefits. Different parts of okra including its mucilage have been currently studied for its role in various therapeutic applications. Therefore, we aimed to develop and characterize the okra mucilage biopolymer (OMB) for its physicochemical properties as well as to evaluate its in vitro antidiabetic activity. The characterization of OMB using Fourier-transform infrared spectroscopy (FT-IR) revealed that okra mucilage containing polysaccharides lies in the bandwidth of 3279 and 1030 cm⁻¹, which constitutes the fingerprint region of the spectrum. In addition, physicochemical parameters such as percentage yield, percentage solubility, and swelling index were found to be 2.66%, 96.9%, and 5, respectively. A mineral analysis of newly developed biopolymers showed a substantial amount of calcium (412 mg/100 g), potassium (418 mg/100 g), phosphorus (60 mg/100 g), iron (47 mg/100 g), zinc (16 mg/100 g), and sodium (9 mg/100 g). The significant antidiabetic potential of OMB was demonstrated using α-amylase and α-glucosidase enzyme inhibitory assay. Further investigations are required to explore the newly developed biopolymer for its toxicity, efficacy, and its possible utilization in food, nutraceutical, as well as pharmaceutical industries.     

Antimicrobial,Antioxidant, Anti-Acetylcholinesterase,Antidiabetic, and Pharmacokinetic Properties of Carum carvi L. and Coriandrum sativum L. Essential Oils Alone and in Combination

Herbs and spices have been used since antiquity for their nutritional and health properties, as well as in traditional remedies for the prevention and treatment of many diseases. Therefore, this study aims to perform a chemical analysis of both essential oils (EOs) from the seeds of Carum carvi (C. carvi) and Coriandrum sativum (C. sativum) and evaluate their antioxidant, antimicrobial, anti-acetylcholinesterase, and antidiabetic activities alone and in combination. Results showed that the EOs mainly constitute monoterpenes with γ-terpinene (31.03%), β-pinene (18.77%), p-cymene (17.16%), and carvone (12.20%) being the major components present in C. carvi EO and linalool (76.41%), γ-terpinene (5.35%), and α-pinene (4.44%) in C. sativum EO. In comparison to standards, statistical analysis revealed that C. carvi EO showed high and significantly different (p < 0.05) antioxidant activity than C. sativum EO, but lower than the mixture. Moreover, the mixture exhibited two-times greater ferric ion reducing antioxidant power (FRAP) (IC₅₀ = 11.33 ± 1.53 mg/mL) and equipotent chelating power (IC₅₀ = 31.33 ± 0.47 mg/mL) than the corresponding references, and also potent activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC₅₀ = 19.00 ± 1.00 mg/mL), β-carotene (IC₅₀ = 11.16 ± 0.84 mg/mL), and superoxide anion (IC₅₀ = 10.33 ± 0.58 mg/mL) assays. Antimicrobial data revealed that single and mixture EOs were active against a panel of pathogenic microorganisms, and the mixture had the ability to kill more bacterial strains than each EO alone. Additionally, the anti-acetylcholinesterase and α-glucosidase inhibitory effect have been studied for the first time, highlighting the high inhibition effect of AChE by C. carvi (IC₅₀ = 0.82 ± 0.05 mg/mL), and especially by C. sativum (IC₅₀ = 0.68 ± 0.03 mg/mL), as well as the mixture (IC₅₀ = 0.63 ± 0.02 mg/mL) compared to the reference drug, which are insignificantly different (p > 0.05). A high and equipotent antidiabetic activity was observed for the mixture (IC₅₀ = 0.75 ± 0.15 mg/mL) when compared to the standard drug, acarbose, which is about nine times higher than each EO alone. Furthermore, pharmacokinetic analysis provides some useful insights into designing new drugs with favorable drug likeness and safety profiles based on a C. carvi and C. sativum EO mixture. In summary, the results of this study revealed that the combination of these EOs may be recommended for further food, therapeutic, and pharmaceutical applications, and can be utilized as medicine to inhibit several diseases.     

Lyophilised Platelet-Rich Fibrin: Physical and Biological Characterisation

Background: Platelet-rich fibrin (PRF) has gained popularity in craniofacial surgery, as it provides an excellent reservoir of autologous growth factors (GFs) that are essential for bone regeneration. However, the low elastic modulus, short-term clinical application, poor storage potential and limitations in emergency therapy use restrict its more widespread clinical application. This study fabricates lyophilised PRF (Ly-PRF), evaluates its physical and biological properties, and explores its application for craniofacial tissue engineering purposes. Material and methods: A lyophilisation method was applied, and the outcome was evaluated and compared with traditionally prepared PRF. We investigated how lyophilisation affected PRF’s physical characteristics and biological properties by determining: (1) the physical and morphological architecture of Ly-PRF using SEM, and (2) the kinetic release of PDGF-AB using ELISA. Results: Ly-PRF exhibited a dense and homogeneous interconnected 3D fibrin network. Moreover, clusters of morphologically consistent cells of platelets and leukocytes were apparent within Ly-PRF, along with evidence of PDGF-AB release in accordance with previously reports. Conclusions: The protocol established in this study for Ly-PRF preparation demonstrated versatility, and provides a biomaterial with growth factor release for potential use as a craniofacial bioscaffold.     

Enhancing the Decolorization of Methylene Blue Using a Low-Cost Super-Absorbent Aided by Response Surface Methodology

The presence of organic dyes from industrial wastewater can cause pollution and exacerbate environmental problems; therefore, in the present work, activated carbon was synthesized from locally available oil palm trunk (OPT) biomass as a low-cost adsorbent to remove synthetic dye from aqueous media. The physical properties of the synthesized oil palm trunk activated carbon (OPTAC) were analyzed by SEM, FTIR-ATR, and XRD. The concurrent effects of the process variables (adsorbent dosage (g), methylene blue (MB) concentration (mg/L), and contact time (h)) on the MB removal percentage from aqueous solution were studied using a three-factor three-level Box–Behnken design (BBD) of response surface methodology (RSM), followed by the optimization of MB adsorption using OPTAC as the adsorbent. Based on the results of the analysis of variance (ANOVA) for the three parameters considered, adsorbent dosage (X₁) is the most crucial parameter, with an F-value of 1857.43, followed by MB concentration (X₂) and contact time (X₃) with the F-values of 95.60 and 29.48, respectively. Furthermore, the highest MB removal efficiency of 97.9% was achieved at the optimum X₁, X₂, and X₃ of 1.5 g, 200 mg/L, and 2 h, respectively.     

Beneficial Effects of Green Tea Catechins on Female Reproductive Disorders: A Review

Tea is one of the most widely consumed beverages worldwide after water, and green tea accounts for 20% of the total tea consumption. The health benefits of green tea are attributed to its natural antioxidants, namely, catechins, which are phenolic compounds with diverse beneficial effects on human health. The beneficial effects of green tea and its major bioactive component, (−)-epigallocatechin-3-gallate (EGCG), on health include high antioxidative, osteoprotective, neuroprotective, anti-cancer, anti-hyperlipidemia and anti-diabetic effects. However, the review of green tea’s benefits on female reproductive disorders, including polycystic ovary syndrome (PCOS), endometriosis and dysmenorrhea, remains scarce. Thus, this review summarises current knowledge on the beneficial effects of green tea catechins on selected female reproductive disorders. Green tea or its derivative, EGCG, improves endometriosis mainly through anti-angiogenic, anti-fibrotic, anti-proliferative and proapoptotic mechanisms. Moreover, green tea enhances ovulation and reduces cyst formation in PCOS while improving generalised hyperalgesia, and reduces plasma corticosterone levels and uterine contractility in dysmenorrhea. However, information on clinical trials is inadequate for translating excellent findings on green tea benefits in animal endometriosis models. Thus, future clinical intervention studies are needed to provide clear evidence of the green tea benefits with regard to these diseases.     

Multi-Targeted Molecular Docking,Pharmacokinetics, and Drug-Likeness Evaluation of Okra-Derived Ligand Abscisic Acid Targeting Signaling Proteins Involved in the Development of Diabetes

Diabetes mellitus is a global threat affecting millions of people of different age groups. In recent years, the development of naturally derived anti-diabetic agents has gained popularity. Okra is a common vegetable containing important bioactive components such as abscisic acid (ABA). ABA, a phytohormone, has been shown to elicit potent anti-diabetic effects in mouse models. Keeping its anti-diabetic potential in mind, in silico study was performed to explore its role in inhibiting proteins relevant to diabetes mellitus- 11β-hydroxysteroid dehydrogenase (11β-HSD1), aldose reductase, glucokinase, glutamine-fructose-6-phosphate amidotransferase (GFAT), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and Sirtuin family of NAD(+)-dependent protein deacetylases 6 (SIRT6). A comparative study of the ABA-protein docked complex with already known inhibitors of these proteins relevant to diabetes was compared to explore the inhibitory potential. Calculation of molecular binding energy (ΔG), inhibition constant (pKi), and prediction of pharmacokinetics and pharmacodynamics properties were performed. The molecular docking investigation of ABA with 11-HSD1, GFAT, PPAR-gamma, and SIRT6 revealed considerably low binding energy (ΔG from −8.1 to −7.3 Kcal/mol) and predicted inhibition constant (pKi from 6.01 to 5.21 µM). The ADMET study revealed that ABA is a promising drug candidate without any hazardous effect following all current drug-likeness guidelines such as Lipinski, Ghose, Veber, Egan, and Muegge.     

Computational Approaches for the Design of Novel Anticancer Compounds Based on Pyrazolo[3,4-d]pyrimidine Derivatives as TRAP1 Inhibitor

In the present in-silico study, various computational techniques were applied to determine potent compounds against TRAP1 kinase. The pharmacophore hypothesis DHHRR_1 consists of important features required for activity. The 3D QSAR study showed a statistically significant model with R² = 0.96 and Q² = 0.57. Leave one out (LOO) cross-validation (R² CV = 0.58) was used to validate the QSAR model. The molecular docking study showed maximum XP docking scores (−11.265, −10.532, −10.422, −10.827, −10.753 kcal/mol) for potent pyrazole analogs (42, 46, 49, 56, 43), respectively, with significant interactions with amino acid residues (ASP 594, CYS 532, PHE 583, SER 536) against TRAP1 kinase receptors (PDB ID: 5Y3N). Furthermore, the docking results were validated using the 100 ns MD simulations performed for the selected five docked complexes. The selected inhibitors showed relatively higher binding affinities than the TRAP1 inhibitor molecules present in the literature. The ZINC database was used for a virtual screening study that screened ZINC05297837, ZINC05434822, and ZINC72286418, which showed similar binding interactions to those shown by potent ligands. Absorption, distribution, metabolism, and excretion (ADME) analysis showed noticeable results. The results of the study may be helpful for the further development of potent TRAP1 inhibitors     

Development of Antibacterial,Degradable and pH-Responsive Chitosan/Guar Gum/Polyvinyl Alcohol Blended Hydrogels for Wound Dressing

The present research is based on the fabrication preparation of CS/PVA/GG blended hydrogel with nontoxic tetra orthosilicate (TEOS) for sustained paracetamol release. Different TEOS percentages were used because of their nontoxic behavior to study newly designed hydrogels’ crosslinking and physicochemical properties. These hydrogels were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and wetting to determine the functional, surface morphology, hydrophilic, or hydrophobic properties. The swelling analysis in different media, degradation in PBS, and drug release kinetics were conducted to observe their response against corresponding media. The FTIR analysis confirmed the components added and crosslinking between them, and surface morphology confirmed different surface and wetting behavior due to different crosslinking. In various solvents, including water, buffer, and electrolyte solutions, the swelling behaviour of hydrogel was investigated and observed that TEOS amount caused less hydrogel swelling. In acidic pH, hydrogels swell the most, while they swell the least at pH 7 or higher. These hydrogels are pH-sensitive and appropriate for controlled drug release. These hydrogels demonstrated that, as the ionic concentration was increased, swelling decreased due to decreased osmotic pressure in various electrolyte solutions. The antimicrobial analysis revealed that these hydrogels are highly antibacterial against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram negative (Pseudomonas aeruginosa and Escherichia coli) bacterial strains. The drug release mechanism was 98% in phosphate buffer saline (PBS) media at pH 7.4 in 140 min. To analyze drug release behaviour, the drug release kinetics was assessed against different mathematical models (such as zero and first order, Higuchi, Baker–Lonsdale, Hixson, and Peppas). It was found that hydrogel (CPG2) follows the Peppas model with the highest value of regression (R² = 0.98509). Hence, from the results, these hydrogels could be a potential biomaterial for wound dressing in biomedical applications.