Thioquinoline derivatives conjugated to thiosemicarbazide as potent tyrosinase inhibitors with anti-melanogenesis properties

Abstract

In the present study, a series of aryl-substituted thioqunoline conjugated to thiosemicarbazide were rationally designed and synthesized. The formation of target compounds was confirmed by spectral characterization techniques such as IR, 1H-NMR, 13C-NMR, ESI–MS, and elemental analysis. Among the synthesized derivatives, compound 10g bearing para-chlorophenyl moiety was proved to be the most potent tyrosinase inhibitor with an IC50 value of 25.75 ± 0.19 µM. Compound 10g as the most potent derivative exhibited a noncompetitive inhibition pattern against tyrosinase in the kinetic study. Furthermore, the in silico cavity detection, as well as the molecular docking assessments, were performed to follow the behavior of 10g within the proposed binding site. Besides, the toxicity of 10g and its potency to reduce the melanin content on A375 cell lines were also measured. Consequently, aryl-substituted thioqunolines conjugated to thiosemicarbazide might be a promising candidate in the cosmetics, medicine, and food industry as tyrosinase inhibitors.

Quinoline-based α-glucosidase inhibitors: synthesis, in vitro potency of inhibition, enzyme kinetics and in silico studies

“…Molecular dynamics simulations were performed using Desmond from the Schrodinger Maestro interface (10), based on the results of the previous docking stage. An orthorhombic cell was de ned and lled with TIP3P model water molecules, and adequate Na ions were added to the system to neutralize the overall charge of the complex.…”

“…Synthetic and natural products containing quinoline structure representing diverse pharmacological activities such as anti-biotic [1], anti-cancer [2], anti-fungal [3], anti-malarial [4], anti-bacterial [5], anti-HIV [6], anti-rheumatoid arthritis [7], anti-tuberculosis [8], anti-diabetic [9], anti-oxidant [10], antiin ammatory [11]. Introducing chloroquine as anti-malaria began a new era of quickly developing drugs like pamaquine, cipro oxacin, camptothecin, topotecan.…”

“…Quinoline pharmacophore, which has strong interactions with the active site of αglucosidase, is well known for its inhibitory activities (Compounds A-D). Also, thiazoles and benzothiazoles (Compounds E, F) has been represented as α-glucosidase inhibitors [10,[23][24][25][26][27] for their ability of providing leads with easy synthetic protocol and structural diversity that make ideal framework in antidiabetic drug discovery (pioglitazone and rosiglitazone) (Figure 1).…”

Synthesis, in vitro α-glucosidase inhibitory activities, and molecular dynamic simulations of novel 4-hydroxyquinolinone-hydrazones as potential antidiabetic agents

“…Nitrogen-containing compounds such as hydroxyquinolinone scaffolds are important structures found in many pharmaceutically active compounds with drug-like properties, which provide high-quality leads and compound libraries 11 , 12 . They are structurally diverse and possess a variety of biological activities such as anticancer, antimicrobial 13 , metal chelator 14 , antialzheimer 15 , and antifungal activities 16 , 17 .…”

Tetrahedral framework nucleic acid loaded with glabridin: A transdermal delivery system applicated to anti‐hyperpigmentation

“…Relying on its biological and structural properties for cell penetration, tFNA can adopt lower electrostatic repulsion to enter cells through cavernous protein internalization 36,41–43 . Further studies have also found that tFNA can pass through the skin barrier smoothly through skin attachments and has a high tissue penetration capacity 31 . Thus tFNA can reach deep tissues in a non‐invasive manner.…”