ABSTRACT
A novel series of N-phenylacetamide-oxindole-thiosemicarbazide hybrids were synthesized and evaluated for their tyrosinase inhibitory activity. According to tyrosinase inhibition results, all the synthesized compounds showed high tyrosinase inhibitory activity with IC50 values ranging from 0.8 to 3.88â µM in comparison to positive control kojic acid with IC50 value of 36.32â µM. Among tested compounds, analog 7o, containing the 2-methyl-4-nitrophenyl on N-phenylacetamide moiety displayed superior tyrosinase inhibition. This compound was around 45-fold more potent than kojic acid. The kinetic analysis of compound 7o demonstrated that this compound is a competitive inhibitor against tyrosinase. Docking study of this compound demonstrated that compound 7o interacted with critical histidine residues within tyrosinase active site.
Subject(s)
Agaricales , Monophenol Monooxygenase , Enzyme Inhibitors/chemistry , Kinetics , Molecular Docking Simulation , Molecular Structure , Oxindoles , Semicarbazides , Structure-Activity RelationshipABSTRACT
Melanin pigment and melanogenesis are a two-edged sword. Melanin has a radioprotection role while melanogenesis has undesirable effects. Targeting the melanogenesis pathway, a series of kojyl thioether conjugated to different quinazolinone derivatives were designed, synthesized, and evaluated for their inhibitory activity against mushroom tyrosinase. All the synthesized compounds were screened for their anti-tyrosinase activity and all derivatives displayed better potency than kojic acid as the positive control. In this regard, 5j and 5h as the most active compounds showed an IC50 value of 0.46 and 0.50 µM, respectively. In kinetic evaluation against tyrosinase, 5j depicted an uncompetitive inhibition pattern. Designed compounds also exhibited mild antioxidant capacity. Moreover, 5j and 5h achieved good potency against the B16F10 cell line to reduce the melanin content, whilst showing limited toxicity against malignant cells. The proposed binding mode of new inhibitors evaluated through molecular docking was consistent with the results of structure-activity relationship analysis.
Subject(s)
Antineoplastic Agents/pharmacology , Biological Products/pharmacology , Enzyme Inhibitors/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Pyrones/pharmacology , Quinazolinones/pharmacology , Sulfhydryl Compounds/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Biological Products/chemical synthesis , Biological Products/chemistry , Biphenyl Compounds/antagonists & inhibitors , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Mice , Molecular Docking Simulation , Molecular Structure , Monophenol Monooxygenase/metabolism , Picrates/antagonists & inhibitors , Pyrones/chemical synthesis , Pyrones/chemistry , Quinazolinones/chemistry , Structure-Activity Relationship , Sulfhydryl Compounds/chemistryABSTRACT
Nowadays, application of vinylazides as precursors is a key method for the construction of N-heterocycles in organic synthesis. These versatile three-atom synthons can be converted into intermediates such as 2H-azirines, iminyl radicals, iminyl metal complexes, iminyl inions and nitrilium ions that subsequently afford a wide range of polyfunctional cyclic nitrogen-containing compounds. In this review, the reactions of vinylazides leading to these products (in the last decade) are categorized based on the types of the resulting N-heterocyclic rings and a brief and concise description of the reaction mechanisms is presented.
Subject(s)
Heterocyclic Compounds , Chemistry Techniques, SyntheticABSTRACT
Thiophene-based analogs have been fascinated by a growing number of scientists as a potential class of biologically active compounds. Furthermore, they play a vital role for medicinal chemists to improve advanced compounds with a variety of biological effects. The current review envisioned to highlight some recent and particularly remarkable examples of the synthesis of thiophene derivatives by heterocyclization of various substrates from 2012 on.