Current Enzyme Inhibition - Volume 21, Issue 1, 2025

The green synthesis of gold nanoparticles (AuNPs) using natural materials has gained significant attention in recent years due to their eco-friendliness and potential applications in various fields.

The present study aimed at the green synthesis and anti-hyperpigmentation potential of gold nanoparticles (AuNPs) using a methanolic extract of Bauhinia vahlii. Furthermore, the green synthesis of the AuNPs was confirmed by UV-visible, FT-IR, XRD, and EMDEX analysis. The size and surface topological significance of green synthesized AuNPs were evaluated through Scanning Electron Microscope and Field Emission Scanning Electron Microscopy.

The size of the synthesized AuNPs was found to be in the range of 100-1000 nm. The tyrosinase inhibitory activity of AuNPs was evaluated through the mushroom tyrosinase inhibitory assay method. The tyrosinase inhibitory activities of crude extract, AuNPs, and Kojic acid were found to be 98.7 ± 0.7, 75 ± 1.3 and 41 ± 1.1 μg/ml, respectively.

Hence, green synthesized AuNPs of B. vahlii leaf extract may be used as a potent anti-hyperpigmentation agent in the market of nano cosmeceuticals.

Pyrroles are biologically active scaffolds that can have a number of different effects. They also have unique pharmacophores inside their ring system that make it easier to make molecules that are more active. Significantly, in the past ten years, research has been conducted on the anti-bacterial properties, with a particular emphasis on drug-resistant Gram-positive and Gram-negative pathogens such as mycobacteria. Additionally, scaffolds based on pyrroles were utilized in the production of anti-tumor medicines that function by modulating or suppressing genes.

This research aimed to create new pyrrole derivatives by chemical means and evaluate their antimicrobial and anticancer properties.

By reacting diverse 1H-pyrrole-2-carbohydrazide derivatives with benzaldehyde under normal conditions, a number of pyrrole variations were created. IR, mass spectroscopy, NMR, and elemental analysis were used to characterize the synthesized compounds. The serial dilution method was used to assess antimicrobial activity, along with a molecular docking study against the enzyme α-topoisomerase II (α-Topo II), which effectively controls the topology of DNA. This enzyme is strongly expressed in rapidly dividing cells and is crucial for transcription, replication, and chromosome structure. Pyrrole and its synthetic derivatives are known to exhibit strong anticancer activity by specifically targeting α-Topo II, which has led multiple researchers to investigate α-Topo II inhibitors as potential anticancer medicines. Consequently, designing pyrroline derivatives is interesting since the succinimide portion of the joined heteroaromatic molecule can selectively engage with the ATP binding pocket via the hydrogen bond network. Newer synthesized compounds were also docked via Schrodinger 2022-4 into the active pocket of the three-dimensional crystallographic structure of the ATP site of human topoisomerase IIα (htopo IIα) (PDB ID: 1zxm).

Among the newly synthesized pyrrole derivatives, compounds demonstrated significant anti-microbial activity. In addition, the AutoDock Vina application was used to perform in-silico docking computations. Compounds 1a and 1h were found to have a stronger antiproliferative effect than compounds against MCF-07 breast cancer cell linen our study, ligands 1a and 1b exhibited better binding energies of -5.049 and -5.035 kcal/mol, respectively. Most of the synthesized pyrrole derivatives showed promising antiproliferative effects; however, further in vivo investigations are needed to confirm or refute these results.

The results of this investigation show that pyrrole derivatives have the potential to be effective antimicrobial and anticancer agents. While resolving safety issues, the structural alterations carried out in this study enhanced the compounds' medicinal capabilities. To clarify the underlying mechanisms of action and enhance the pharmacological characteristics of these new pyrrole derivatives, further research is necessary.

Diabetes prevalence is progressively rising everywhere, particularly in developing countries. Lichens have evolved into a rich source of innovative bioactive chemicals with their anti-oxidant capabilities, widening the scope of well-documented and effective diabetes treatment.

The main objectives of this study were to perform in vitro alpha-amylase, alpha-glucosidase inhibition analysis, and anti-oxidant of lichen Physica aipolia.

Folin Ciocalteu’s reagent was used to determine the total phenolic content for biological activities. The Aluminum trichloride method was used to determine total flavonoid content, and the free radical assay method was used to determine the antioxidant activity of P. aipolia using 2,2-diphenyl-1-picrylhydrazyl (DPPH). Moreover, substrate 2-Chloro-4-nitrophenyl-α-D-maltotrioside (CNPG3) and substrate-nitrophenyl-α-D-glucopyranose (p-NPG) were used for the determination of alpha-amylase and alpha-glucosidase inhibition activities respectively, and molecular docking was performed by Auto Dock Vina.

Total phenolic and flavonoid contents present in P. aipolia were 37.41 ± 2.87 mg GAE/g and 5.53 ± 0.95 mg QE/g, respectively. For anti-oxidant inhibition activity, crude extract of methanol showed an IC50 value of 15.324 ± 0.80 µg/mL. Furthermore, a methanolic crude extract showed significant inhibition activities against alpha-amylase (IC50 = 178.50 ± 1.10 µg/mL) and alpha-glucosidase (IC50 = 76.10 ± 0.91 µg/mL). During in silico analysis, zeorin showed an effective binding affinity with -7.9 kcal/mol, and Atranorin showed -7.4 kcal/mol in the orthosteric site of the protein.

Physica aipolia exhibits the potential to impact biological functions, demonstrating antidiabetic properties, as confirmed by molecular docking analysis in silico.

The present study highlights the comparative therapeutic efficacy of the newly synthesized drug 17-Oximino-5-androsten-3β-yl 4-aminobenzoate (17a-aza steroid) and finasteride for the treatment of experimentally induced prostate carcinogenesis in rats. Considering the inhibitory activity of the oximes to 5α-reductase and the role of the ester group in augmenting the anti-androgenic property, we decided to synthesize a compound with a lactam moiety in ring D and esters at 3β position of androsterone nucleus as a more potent 5α-reductase inhibitor.

In this study, 30 Sprague Dawley (SD) rats were divided into six groups, viz. Group I as normal controls, Group II was treated with carcinogen N-methyl-N-nitrosourea (MNU) and hormone testosterone propionate (TP) for inducing prostate cancer, Group III rats were treated with finasteride (10 mg/Kg of body weight for 8 weeks through oral gavage), Group IV was treated with 17a-aza steroid (10 mg/Kg of body weight for 8 weeks through oral gavage), whereas, Group V and Group VI were given finasteride and 17a-aza steroid, respectively, with similar doses as in Group III and IV after pretreatment with a carcinogen (MNU) and hormone (TP).

The induction of carcinogenesis by treating animals with MNU+TP revealed a significant reduction in weight loss as compared to the normal control group, which, however, increased following 17a-aza steroid treatment. Furthermore, the study witnessed a significant improvement in prostatic biomarker, viz prostatic acid phosphatase (PAcP) in serum following finasteride and 17a-aza steroid treatment to MNU+TP treated rats. Histological investigation of prostate tissue sections of 17a-aza steroid-treated prostate cancer rats showed milder hyperplastic glandular epithelium and exhibited signs of recovery as compared to carcinogen-treated rats.

The present findings are preliminary and suggest that the 17a-aza steroid has therapeutic efficacy for the management of experimentally induced prostate cancer, as evidenced by changes in prostate weight, PAcP levels, and histology. In comparison to finasteride, further exploration is needed to assertively conclude its comparative therapeutic efficacy.

A 2D QSAR study of acyl-coenzyme A (CoA): cholesterol acyltransferase (ACAT) inhibitors revealed that electronic, topological, and steric properties are important structural features required for activity against ACAT.

In order to interpret the evidence encrypted by the molecular structure of the compounds, a standard physicochemical descriptors-centered, and Quantitative Structure-Activity Relationship (QSAR) approach was implemented on a data set of Indoline derivatives were reported to be acyl-coenzyme A (CoA): cholesterol acyltransferase ACAT inhibitors.

The ACAT enzyme plays an important role in the absorption of dietary cholesterol. Therefore, the inhibition of ACAT is a key strategy or primary objective for the treatment of hypercholesterolemia and atherosclerosis.

Chemo metric models were designed by inserting a battery of statistical techniques in the current study that demonstrate the linear approaches of analysis, including multiple linear regression (MLR), partial least square PLS, and non-linear methods such as artificial neural networks (ANN).

The activity contributions of these molecules were analyzed through regression equation, and the best QSAR model was created with an excellent correlative and predictive ability. Significant statistical values S = 0.35, F = 60.30, r = 0.92, r² = 0.85, r² (CV) = 0.82 of the designed models were obtained using stepwise MLR and a comparable PLS and FFNN model with r² (CV) = 0.82, 0.88 and 0.86 respectively and the relevant descriptors like inertia moment 1 size, Kier Chiv4 (cluster) index, Kier Chiv6(ring) index offered important information regarding this model.

The model reveals that inertia moment 1 size, Kier Chiv4 (cluster) index, and Kier Chiv6 (ring) index are prerequisite descriptors to determine other promising ACAT antagonists with high and liable potency against the target. Therefore, these characteristics may be used efficiently for the design and evaluation of active compounds as new ACAT inhibitors thanks to their utilization.

The present study aimed to explore the hepatorenal efficacy of ethanolic and hydroalcoholic extract against Gentamicin and Cisplatin-induced toxicity in experimental rats.

The current research focuses on the characterization and evaluation of the hepatorenal efficacy of P. granatum extracts on cellular and tissue models, particularly in terms of its restorative actions following cytotoxic damage induced by Gentamicin and Cisplatin. This work builds upon several key areas of contemporary scientific research.

The objective of the current investigation was to establish an association of oxidative stress in hepatorenal insufficiency caused by Gentamicin and Cisplatin xenobiotics and its amelioration with the antioxidant activity of ethanolic extract of Punica granatum (EEPG) and hydroalcoholic extract of Punica granatum (HAEPG).

Using ascorbic acid as a standard, the in vitro antioxidant activity of EEPG and HAEPG was assessed using the DPPH method. The hepatorenal efficiency of the EEPG and HAEPG were studied in Gentamicin and Cisplatin-induced models. The hepatorenal toxicity was induced by 100 mg/kg/day i.p. of Gentamicin for 12 days and 1.5 mg/kg/day i.p. cisplatin for 3 weeks in Wistar albino rats. Lipid profile, serum hepatorenal markers, and hepatorenal tissue oxidative markers such as, CAT, MDA, GSH, and SOD were estimated to assess the extent of hepatorenal efficiency. Using Masson trichrome (MT) stained tissue sections, renal and hepatic tissue damage was assessed. The degree of renal tissue damage was evaluated using tubular necrosis, perivascular edema, intratubular proteinaceous cast, and vascular congestion.

In vitro studies have shown that the HAEPG containing higher total phenolic and flavonoid content, exhibits greater antioxidant activity compared to the EEPG. The severity of hepatotoxicity and renal toxicity was found to be more severe in cisplatin than Gentamicin. The Cisplatin treatment more severely affects the level of CAT, GSH, and SOD, respectively compared to Gentamicin induction. Cisplatin also significantly decreased SOD and increased MDA levels. Treatment with EEPG and HAEPG demonstrated beneficial effects by reducing the levels of oxidative enzymes, which contributes to the restoration of hepatorenal damage due to their antioxidant properties. The MT panels of the treated groups revealed and supported hepatorenal regenerative changes.

The antioxidant properties of EEPG and HAEPG showed beneficial effects and ameliorated the levels of tissue hepatorenal oxidative enzymes and were found to possess restoration of hepatorenal damage in a dose-dependent manner.