Design, synthesis, and in vitro and in silico study of 1-benzyl-indole hybrid thiosemicarbazones as competitive tyrosinase inhibitors.

Autor:	Batool Z; Institute of Chemical Sciences, Bahauddin Zakariya University Multan-60800 Pakistan zahidshafiq@bzu.edu.pk., Ullah S; Natural and Medical Sciences Research Centre, University of Nizwa P.O. Box 33, PC 616, Birkat Al Mauz Nizwa Sultanate of Oman aharrasi@unizwa.edu.om., Khan A; Natural and Medical Sciences Research Centre, University of Nizwa P.O. Box 33, PC 616, Birkat Al Mauz Nizwa Sultanate of Oman aharrasi@unizwa.edu.om.; Department of Chemical and Biological Engineering, College of Engineering, Korea University 145 Anam-ro, Seongbuk-gu Seoul 02841 Republic of Korea., Siddique F; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakariya University Multan-60800 Pakistan., Nadeem S; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakariya University Multan-60800 Pakistan.; Department of Pharmacy, The Women University Multan 60000 Pakistan., Alshammari A; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University Post bezBox 2455 Riyadh 11451 Saudi Arabia., Albekairi NA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University Post bezBox 2455 Riyadh 11451 Saudi Arabia., Talib R; Institute of Chemical Sciences, Bahauddin Zakariya University Multan-60800 Pakistan zahidshafiq@bzu.edu.pk., Al-Harrasi A; Natural and Medical Sciences Research Centre, University of Nizwa P.O. Box 33, PC 616, Birkat Al Mauz Nizwa Sultanate of Oman aharrasi@unizwa.edu.om., Shafiq Z; Institute of Chemical Sciences, Bahauddin Zakariya University Multan-60800 Pakistan zahidshafiq@bzu.edu.pk.
Jazyk:	angličtina
Zdroj:	RSC advances [RSC Adv] 2024 Sep 06; Vol. 14 (39), pp. 28524-28542. Date of Electronic Publication: 2024 Sep 06 (Print Publication: 2024).
DOI:	10.1039/d4ra05015k
Abstrakt:	Developing new anti-tyrosinase drugs seems crucial for the medical and industrial fields since irregular melanin synthesis is linked to the resurgence of several skin conditions, including melanoma, and the browning of fruits and vegetables. A novel series of N-1 and C-3 substituted indole-based thiosemicarbazones 5(a-r) are synthesized and further analyzed for their inhibition potential against tyrosinase enzyme through in vitro assays. The synthesized compounds displayed very good to moderate inhibition with half maximal inhibitory concentration in the range of 12.40 ± 0.26 μM to 47.24 ± 1.27 μM. Among all the derivatives 5k displayed the highest inhibitory activity. According to SAR analysis, the derivatives with 4-substitution at the benzyl or phenyl ring of the thiosemicarbazones exhibited better inhibitory potential against tyrosinase. In silico analysis (including ADMET prediction and molecular docking) was conducted and compared with the standard drug (kojic acid). These findings may help the hunt for new melanogenesis inhibitors that the food and cosmetics industries may find valuable. Competing Interests: The authors have declared no conflict of interest. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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