Akademik Veri Yönetim Sistemi
Naunyn-Schmiedeberg's Archives of Pharmacology, 2026 (SCI-Expanded, Scopus)
The discovery of single-molecule therapeutics capable of simultaneously addressing antibiotic resistance and neurodegeneration represents a critical unmet need in modern medicinal chemistry. Herein, I report the rational design and efficient one-pot synthesis of a novel class of 1,2,3-triazole–thiophene hybrids (2a-2e) as dual-target bioactive agents. This streamlined synthetic approach afforded the target compounds in good yields, with substituent effects playing a decisive role in reaction efficiency. Biological evaluation revealed a pronounced enhancement in antibacterial activity, with several compounds exhibiting potent efficacy against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MRSA). In particular, compounds 2d and 2e demonstrated remarkable potency, achieving minimum inhibitory concentration (MIC) values as low as 2 µg/mL against MRSA. Structure–activity relationship analysis identified para-halogen substitution as a key determinant of antibacterial performance. Beyond their antibacterial effects, the hybrids displayed significant acetylcholinesterase (AChE) inhibitory activity, with compounds 2c (IC50 = 25.914 ± 0.061 µg/mL) and 2d (IC50 = 27.664 ± 0.238 µg/mL) emerging as the most active analogues. Complementary antioxidant assays further underscored the multifunctional character of these scaffolds. Molecular docking studies provided mechanistic support for the experimental findings, revealing favorable binding modes within the AChE active site. Collectively, this work establishes 1,2,3-triazole–thiophene hybrids as a versatile and previously underexplored scaffold for dual-target drug design. The identified lead compounds (2c-2e) demonstrate compelling potential for further optimization toward integrated therapeutic strategies against antibiotic-resistant infections and neurodegenerative disorders.