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The present study describes the discovery of novel inhibitors of mushroom tyrosinase enzyme. For that purpose, a series of varyingly substituted 2-phenylchromone analogues 1–28 were synthesized and characterized in detail by various spectroscopic techniques (UV–Vis, FTIR, 1H NMR, 13C NMR) and mass spectrometry. All the derivatives (1–28) were screened in vitro for their inhibitory potential against mushroom tyrosinase enzyme. Interestingly, all the synthetic compounds displayed good to excellent inhibitory activity with IC50 values ranging from 0.093 ± 0.003 μg/ml to 23.58 ± 0.94 μg/ml for brominated 3-hydroxy-2-phenylchromones and 0.22 ± 0.017 μg/ml to 22.22 ± 1.1 μg/ml for brominated 2-phenylchromones against tyrosinase in comparison to the standard kojic acid (IC50 = 1.79 ± 0.64 μg/ml). Remarkably, the bromine atoms attached on ring A attribute to increases the inhibitory potential of 2-phenylchromone moiety and anti-tyrosinase assay demonstrated that compound 10 (IC50 = 0.093 ± 0.003 µg/ml) was found almost nineteenfold, 11 (IC50 = 0.126 ± 0.015 µg/ml) fourteenfold and 26 (IC50 = 0.22 ± 0.017 µg/ml) about eightfold more active than the positive control. Notably, among the already literature reported tyrosinase inhibitors, these analogues have been found the most active inhibitors of mushroom tyrosinase with the lowest possible IC50 values. To design and develop novel tyrosinase inhibitors using 2-phenylchromone as a structural motif in the future, a limited structure-activity relationship was established. Moreover, in silico studies were carried out to rationalize the binding mode of interactions of all the targeted compounds (1–28) with the active site of enzymes. The experimental and theoretical results are in parallel with one another. In addition, molecular description was performed with the drug-likeness and bioactivity scores. Computational analysis predicted that few compounds are in a linear correlation with Lipinski’s RO5 indicating superb drug-likeness and bioactivity score for drug targets.

Targeting tyrosinase (TYR), a key enzyme responsible for melanogenesis disorders, is a well-known approach utilized for the development of melanogenesis inhibitor. A variety of dermatological disorders and microbial skin infections can cause hyperpigmentation. Hence, exploring new scaffolds for the treatment of melanogenesis disease is an inspiring goal. In this context, a series of varyingly substituted flavone-based hydrazones have been designed, synthesized and characterized successfully. The present study describes the discovery of novel mushroom tyrosinase inhibitors (TIs) for treating hyperpigmentation. In due course, flavone scaffold has been incorporated into the novel chemotypes that exhibit in vitro inhibitory effects against mushroom tyrosinase for the purpose of discovering anti‐melanogenic agents. Biological investigations of prepared analogs herein demonstrated moderate to excellent activity against most of the fungal-bacterial strains and their activity is comparable to those of commercially available antibiotics i.e., Ciprofloxacin and Ketoconazole. Based on in vitro tyrosinase inhibitory assay, some compounds exhibited potent inhibition particularly, 3g (IC50 = 1.40 ± 0.16 µM), 3j (IC50 = 0.95 ± 0.07 µM), 3o (IC50 = 1.13 ± 0.11 µM), and 3q (IC50 = 1.01 ± 0.1 µM) showed best inhibition i.e., 0.7, 0.5, 0.6 and 0.5 folds, respectively, than kojic acid (IC50 = 1.79 ± 0.6 µM). Lineweaver-Burk plots demonstrated that the most potential derivative 3j tyrosinase inhibition proceeds via non-competitive pathway and the Michaelis-Menton constant (Km) value is 0.0265. Molecular modeling was performed for all tested analogs (3a–3q) using a model of mushroom tyrosinase to find crucial binding modes liable for inhibitory activity. The SARs were preliminarily examined, and the docking study revealed that analogs 3j, 3o and 3p had a strong binding association to tyrosinase (2Y9X). Furthermore, a drug-likeness study was employed and confirmed the favorable activity of the new analogs as a new anti-tyrosinase agent.

A small library of flavone-based hydrazones has been designed, synthesized and characterized. In this context, thirteen flavone hydrazones (3a-3 m) were synthesized by the acid-catalyzed condensation of flavone with 2,4-dinitrophenylhydrazine (2,4-DNPH) and characterized by different spectral techniques (IR, UV–Vis, NMR and mass spectrometry). The electrochemical, photophysical and theoretical investigations of such type of compounds are hitherto unknown. The electrochemical behavior of these hydrazones at a platinum electrode has been analyzed by cyclic voltammetry (CV) and was investigated at 200, 100 and 40 mVs−1 in acetonitrile (CH3CN). These hydrazones showed a quasi-reversible redox reaction. The oxidation–reduction reactive sites of these derivatives were located via geometry optimization using density functional theory (DFT) at the B3LYP/3–21 g in the Guassian-09 level of theory. Moreover, the target compounds exhibited interesting fluorescent properties. Owing to their excellent photophysical and redox results, a detailed structure-property relationship was established to assess the substituents impact and their position on the physicochemical and electronic properties. All the experimental results were in accordance with the computational studies.

The present study describes efficient and facile syntheses of varyingly substituted 3-thioaurones from the corresponding 3-oxoaurones using Lawesson's reagent and phosphorous pentasulfide. In comparison, the latter methodology was proved more convenient, giving higher yields and required short and simple methodology. The structures of synthetic compounds were unambiguously elucidated by IR, MS and NMR spectroscopy. All synthetic compounds were screened for their inhibitory potential against in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Molecular docking studies were also performed in order to examine their binding interactions with AChE and BChE human proteins. Both studies revealed that some of these compounds were found to be good inhibitors against AChE and BChE.

To explore new scaffolds for the treat of Alzheimer's disease appears to be an inspiring goal. In this context, a series of varyingly substituted flavonols and 4-thioflavonols have been designed and synthesized efficiently. All the newly synthesized compounds were characterized unambiguously by common spectroscopic techniques (IR, 1H-, 13C NMR) and mass spectrometry (EI-MS). All the derivatives (1-24) were evaluated in vitro for their inhibitory potential against cholinesterase enzymes. The results exhibited that these derivatives were potent selective inhibitors of acetylcholinesterase (AChE), except the compound 11 which was selective inhibitor of butyrylcholinesterase (BChE), with varying degree of IC50 values. Remarkably, the compounds 20 and 23 have been found the most potent almost dual inhibitors of AChE and BChE amongst the series with IC50 values even less than the standard drug. The experimental results in silico were further validated by molecular docking studies in order to find their binding modes with the active pockets of AChE and BChE enzymes.

In this study, a library of new intriguing flavonol derivatives (1–17) was designed and synthesized through a facile route involving Algar-Flynn-Oyamada reaction in a one-pot synthesis. The molecular structures of all newly synthesized compounds were unequivocally corroborated by different spectroscopic techniques such as FTIR, UV–Vis, 1H NMR and 13C NMR and mass spectrometry (EI-MS). All the synthesized analogs (1-17) were evaluated in vitro for their inhibitory potential against ɑ-amylase and ɑ-glucosidase enzymes. Interestingly, all the synthetic compounds displayed good to moderate inhibition potential with IC50 values ranging from 4.86 ± 1.39 to 265.61 ± 5.85 μM for a-amylase, and 70.57 ± 1.13 to 322.98 ± 4.43 μM for a-glucosidase in comparison to the standard acarbose (IC50 = 5.03 ± 9.44 μM for a-amylase and IC50 = 75.26 ± 0.15 μM for α-glucosidase). It is worth mentioning that amongst the series, the compounds 9 (IC50 = 4.86 ± 1.39 μM for a-amylase and IC50 = 70.57 ± 1.13 μM for α-glucosidase) and 14 (IC50 = 5.02 ± 1.35 for a-amylase and IC50 = 71.69 ± 5.85 μM for α-glucosidase) were found the most potent dual inhibitors, even more active than standard. Furthermore, the target compounds (1-17) exhibited moderate to good antioxidant activities. Molecular simulations studies were conducted to correlate the in vitro results and to identify the possible mode of binding interaction of ligands with the active site of enzymes. Moreover, molecular description was performed with the drug-likeness and bioactivity scores. The results showed that some compounds are in a linear correlation with Lipinski’s rule of five demonstrating good drug-likeness and bioactivity score for drug targets. Structure-activity relationships delivered useful insights towards this class of compounds, and thus paved the way to design novel analogs with improved potency.

The prime objective of this research work is to prepare readily soluble synthetic analogues of naturally occurring 3-O-flavonol glycosides and then investigate the influence of various substituents on biological properties of synthetic compounds. In this context, a series of varyingly substituted 3-O-flavonol glycosides have been designed, synthesized and characterized efficiently. The structures of synthetic molecules were unambiguously corroborated by IR, 1H, 13C NMR and ESI-MS spectroscopic techniques. The structure of compound 22 was also analyzed by X-ray diffraction analysis. All the synthetic compounds (21-30) were evaluated for in vitro inhibitory potential against cholinesterase enzymes. The results displayed that most of the derivatives were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with varying degree of IC50 values. The experimental results were further encouraged by molecular docking studies in order to explore their binding behavior with the active pocket of AChE and BChE enzymes. The experimental and theoretical results are in parallel with one another.

Phytochemical investigation of the leaves of Astragalus beckari yielded four flavonol aglycones, namely kaempferol, quercetin, 5-deoxy kaempferol and fisitin. These isolated compounds were then synthesised in the laboratory using the Algar-Flyn-Oyamad reaction. Antioxidant activity of both the isolated and synthesised flavonoids was compared using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay method. The isolated flavonoids were found to be more active.

Synthesis of flavones, 4-thioflavones and 4-iminoflavones was carried out with the substitution of variable halogens, methyl, methoxy and nitro groups in the A, B and AB rings of the respective compounds and we also report here their antibacterial activity. Most of the synthesized compounds were found to be active against Escherichia coli, Bacillus subtilis, Shigella flexnari, Salmonella aureus, Salmonella typhi and Pseudomonas aeruginosa. Activity of 4-thioflavones and 4-iminoflavones was found to be higher than that of their corresponding flavone analogues. Investigated compounds having substituents like F, OMe and NO2 at 4'-position in ring-B exhibited enhanced activity and the presence of electronegative groups in the studied compounds showed a direct relationship to the antibacterial activity.

(R)-alpha-Aminoadipic acid is available on a large scale by enzymatic cleavage from cephalosporin C (CephC) in the production of 7-aminocephalosporanic acid (7-ACA). It can be converted into other interesting enantiomerically pure compounds, e. g. derivatives of (R)-pipecolic acid (R-piperidine-2-carboxylic acid), (R)-6-oxopiperidine-2-carboxylic acid, (R)-1,2,3,4-tetrahydropyridine-2(2H)-carboxylates, and other compounds obtained by further conversions of these products.