Synergistic biomedical potential and molecular docking analyses of coumarin–triazole hybrids as tyrosinase inhibitors: design, synthesis, in vitro profiling, and in silico studies

The tyrosinase enzyme has a vital role in the browning of vegetables and fruits and the biosynthesis of melanin. In this work, we synthesized a diverse library of coumarin–triazole hybrids, and these compounds were characterized by using suitable analytical techniques. Our research work extends beyond the synthetic effort to explore the therapeutic potential of these compounds. We put the synthesized compounds through meticulous in vitro screening against the tyrosinase enzyme, and these coumarin derivatives evinced good IC50 values in the range of 0.339 ± 0.25 µM to 14.06 ± 0.92 µM. In the library of synthesized compounds, six compounds were found to be more potent than standard ascorbic acid (IC50 = 11.5 ± 1.00), and among them, 17e and 17f, being the most active, exhibited remarkable anti-tyrosinase potential, with IC50 values of 0.339 ± 0.25 μM and 3.148 ± 0.23 μM, respectively. Furthermore, an in silico modeling study was carried out to determine the key interactions of these compounds with the tyrosinase protein (PDB ID: 2Y9X) and thus to authenticate our experimental findings. The quantitative SAR studies exhibited a good correlation between the synthesized derivatives of coumarin and their anti-tyrosinase activity. The docking studies verified the experimental results, and ligand 17e showed good interaction with the core residues of tyrosinase. This study not only expands the field of coumarin–triazole hybrid synthesis but also provides valuable insights for the development of novel tyrosinase inhibitors

Discovery of novel 1,2,4-triazole tethered β-hydroxy sulfides as bacterial tyrosinase inhibitors: synthesis and biophysical evaluation through in vitro and in silico approaches

In this study, a series of 1,2,4-triazole-tethered β-hydroxy sulfide scaffolds 11a–h was synthesized in good to remarkable yields (69–90%) through the thiolysis of oxiranes by the thiols in aqueous basic catalytic conditions. The synthesized 1,2,4-triazole-tethered β-hydroxy sulfides were screened against bacterial tyrosinase enzyme, and Gram-positive and Gram-negative bacterial cultures i.e., (S. aureus) Staphylococcus aureus & (E. coli) Escherichia coli. Among the synthesized derivatives, the molecules 11a (IC50 = 7.67 ± 1.00 μM), 11c (IC50 = 4.52 ± 0.09 μM), 11d (IC50 = 6.60 ± 1.25 μM), and 11f (IC50 = 5.93 ± 0.50 μM) displayed the better tyrosinase inhibitory activity in comparison to reference drugs ascorbic acid (IC50 = 11.5 ± 1.00 μM) and kojic acid (IC50 = 30.34 ± 0.75 μM). The molecule benzofuran-triazol-propan-2-ol 11c proved to be the most potent bacterial tyrosinase inhibitory agent with a minimum IC50 of 4.52 ± 0.09 μM, as compared to other synthesized counterparts and both standards (kojic acid and ascorbic acid). The compound diphenyl-triazol-propan-2-ol 11a and benzofuran-triazole-propan-2-ol 11c showed comparable anti-bacterial chemotherapeutic efficacy with minimum inhibitory concentrations (MIC = 2.0 ± 2.25 mg mL−1 and 2.5 ± 0.00 mg mL−1, respectively) against S. aureus bacterial strain in comparison with standard antibiotic penicillin (MIC = 2.2 ± 1.15 mg mL−1). Furthermore, among the synthesized derivatives, only compound 11c demonstrated better anti-bacterial activity (MIC = 10 ± 0.40 mg mL−1) against E. coli, which was slightly less than the standard antibiotic i.e., penicillin (MIC = 2.4 ± 1.00 mg mL−1). The compound 11c demonstrated a better binding score (−7.08 kcal mol−1) than ascorbic acid (−5.59 kcal mol−1) and kojic acid (−5.78 kcal mol−1). Molecular docking studies also validate the in vitro anti-tyrosinase assay results; therefore, the molecule 11c can be the lead bacterial tyrosinase inhibitor as well as the antibacterial agent against both types of bacterial strains after suitable structural modifications

Clinical evaluation of the efficacy of a combination of <i style="">zanjabeel</i> (<i style="">Zingiber officinale</i>) and <i style="">amla</i> (<i style="">Emblica officinalis</i>) in hyperlipidaemia

413-416In Unani System of Medicine, many drugs (single drugs as well compound formulations) are used for the purpose of reducing body weight and treating the obesity (Muhazzil). Indian gooseberry (amla) & ginger (Zanjabeel) are among these medicines. Since these drugs are useful in obesity, these can also be proved beneficial in lowering increased concentration of plasma lipids or treating hyperlipidaemia. Their efficacy has also been proved pharmacologically and these are documented as good hypolipidaemic as well as antioxidant natural agents. The combination of drugs was found to be significant in lowering the level of serum total cholesterol, serum tryglycerides, serum LDL-cholesterol, serum VLDL-cholesterol and in increasing the level of serum HDL-cholesterol in patients of primary hyperlipidaemia

Ultrasonic-Assisted Synthesis of Benzofuran Appended Oxadiazole Molecules as Tyrosinase Inhibitors: Mechanistic Approach through Enzyme Inhibition, Molecular Docking, Chemoinformatics, ADMET and Drug-Likeness Studies

Furan-oxadiazole structural hybrids belong to the most promising and biologically active classes of oxygen and nitrogen containing five member heterocycles which have expanded therapeutic scope and potential in the fields of pharmacology, medicinal chemistry and pharmaceutics. A novel series 5a–j of benzofuran-oxadiazole molecules incorporating S-alkylated amide linkage have been synthesized using ultrasonic irradiation and screened for bacterial tyrosinase inhibition activity. Most of the synthesized furan-oxadiazole structural motifs exhibited significant tyrosinase inhibition activity in the micromolar range, with one of the derivatives being more potent than the standard drug ascorbic acid. Among the tested compounds, the scaffold 5a displayed more tyrosinase inhibition efficacy IC50 (11 ± 0.25 μM) than the ascorbic acid IC50 (11.5 ± 0.1 μM). Compounds 5b, 5c and 5d efficiently inhibited bacterial tyrosinase with IC50 values in the range of 12.4 ± 0.0–15.5 ± 0.0 μM. The 2-fluorophenylacetamide containing furan-oxadiazole compound 5a may be considered as a potential lead for tyrosinase inhibition with lesser side effects as a skin whitening and malignant melanoma anticancer agent

Geranyl flavanone from Feronia limonia (L.) Swingle

Introduction:Feronia limonia (synonyms: Feronia elephantum, Hesperethusa crenulata, Limonia acidissima Linn, Schinus limonia) is a member of Rutaceae family. F. limonia is an aesthetically pleasing plant with various medicinal and nutraceutical properties

Enhanced visible light-driven photocatalytic degradation of crystal violet dye using Cr doped BaFe12O19 prepared via facile micro-emulsion route

The Cr ion doping effect on various properties of Cr doped BaCrxFe12-xO19 nanoparticles was investigated, which were synthesized via a facile microemulsion approach and properties were studied using XRD, SEM, FTIR, Raman, photoluminescence and UV–visible techniques along with dielectric, optical and ferroelectric properties. The BaCrxFe12-xO19 structure was hexagonal involving P63/mmc space group with average crystalline size of 9–18 nm. The NPs exhibited agglomerated platelet heterogeneous morphology. The presence of the Ba-O-Fe functional group was also confirmed by FTIR analysis. The PL analysis revealed that the doping reduced the recombination rate and charge (e−-h+) separation is facilitated. The coercivity (Hc) and saturation polarization (Ps) increased with doping content and dielectric loss reduces with frequency and dopant concentration. The dopant contents also increased the AC conductivity and the optical bandgap found in 1.75–2.83 (eV) range. The BaCrxFe12-xO19 exhibited a significantly higher photocatalytic efficiency versus BaFe12O19, and 91 % CV dye was degraded in 90 min under visible light irradiation. Additionally, a recycling experiment was conducted to confirm the stability of the prepared photocatalyst and Cr doped BaCrxFe12-xO19 exhibited excellent stability and reusability. The Cr doping affected the dielectric, optical and ferroelectric properties and based on photocatalytic properties of BaCrxFe12-xO19, it has potential applications for the destruction of dyes in wastewater under visible light exposure, which will make the process highly feasible for photocatalytic applications

Protease inhibition, in vitro antibacterial and IFD/MM-GBSA studies of ciprofloxacin-based acetanilides.

In this study, we have investigated ciprofloxacin-based acetanilides for their in-vitro inhibitory study against gram +ve, -ve bacteria and serine protease activity. The compounds 4e and 4g showed excellent antibacterial activity against Bacillus subtilis with a zone of inhibition (ZI) values of 40 ± 0.9 mm, 37 ± 1.4 mm and with MIC values of 4.0 ± 0.78 mg/mL, 3.0 ± 0.98 mg/ML respectively, while 4a and 4i were found most active against Escherichia coli, with ZI values 38 ± 0.1 mm, 46 ± 1.8 mm and with MIC values of 1.0 ± 0.25 mg/mL, 1.0 ± 0.23 mg/mL respectively. All derivatives (4a-j) significantly inhibited the catalytic activity of serine protease, while 4a exhibited a maximum (100%) inhibitory effect at 96 minutes having 22.50 minutes [Formula: see text], and non-competitive inhibition with 0.1±0.00μM Ki. The IFD/MM-GBSA studies highlighted the binding mode of 4a for protease inhibition and indicated improved binding affinity with -107.62 kcal/mol of ΔGbind

Genetic Polymorphism in Angiotensinogen and Its Association with Cardiometabolic Diseases

Angiotensinogen (AGT) is one of the most significant enzymes of the renin-angiotensin-aldosterone system (RAAS) which is involved in the regulation and maintenance of blood pressure. AGT is involved in the production of angiotensin I which is then converted into angiotensin II that leads to renal homeostasis. However, various genetic polymorphisms in AGT have been discovered in recent times which have shown an association with various diseases. Genetic polymorphism increases the level of circulating AGT in blood which exaggerates the effects produced by AGT. The associated diseases occur due to various effects produced by increased AGT levels. Several cardiovascular diseases including myocardial infarction, coronary heart disease, heart failure, hypertrophy, etc. are associated with AGT polymorphism. Other diseases such as depression, obesity, diabetic nephropathy, pre-eclampsia, and liver injury are also associated with some variants of AGT gene. The most common variants of AGT polymorphism are M235T and T174M. The two variants are associated with many diseases. Some other variants such as G-217A, A-6G, A-20C and G-152A, are also present but they are not as significant as that of M235T and T174M variants. These variants increase the level of circulating AGT and are associated with prevalence of different diseases. These diseases occur through various pathological pathways, but the initial reason remains the same, i.e., increased level of AGT in the blood. In this article, we have majorly focused on how genetic polymorphism of different variants of AGT gene is associated with the prevalence of different diseases

Further stabilization of alcalase immobilized on glyoxyl supports: amination plus modification with glutaraldehyde

Alcalase was immobilized on glyoxyl 4% CL agarose beads. This permitted to have Alcalase preparations with 50% activity retention versus Boc-l-alanine 4-nitrophenyl ester. However, the recovered activity versus casein was under 20% at 50 °C, as it may be expected from the most likely area of the protein involved in the immobilization. The situation was different at 60 °C, where the activities of immobilized and free enzyme became similar. The chemical amination of the immobilized enzyme or the treatment of the enzyme with glutaraldehyde did not produce any significant stabilization (a factor of 2) with high costs in terms of activity. However, the modification with glutaraldehyde of the previously aminated enzyme permitted to give a jump in Alcalase stability (e.g., with most than 80% of enzyme activity retention for the modified enzyme and less than 30% for the just immobilized enzyme in stress inactivation at pH 7 or 9). This preparation could be used in the hydrolysis of casein at pH 9 even at 67 °C, retaining around 50% of the activity after 5 hydrolytic cycles when the just immobilized preparation was almost inactive after 3 cycles. The modified enzyme can be reused in hydrolysis of casein at 45 °C and pH 9 for 6 cycles (6 h) without any decrease in enzyme activity.This research has been funded by MINECO from Spanish Government, (project number CTQ2017-86170-R).Peer reviewe