Acyl thiourea scaffolds are frequently employed in drug development to discern unique and essential therapies for the eradication of the most challenging diseases. Hence, we developed a library of novel cyclopropyl incorporating acyl thiourea derivatives (4a-j) and evaluated their antimicrobial, α-amylase, and proteinase K inhibition potential. Compound (4h) (4-methoxy) demonstrated the strongest α-amylase inhibition (IC = 1.572 ± 0.017 μM), while compound (4j) (3,4,5-trimethoxy) exhibited potent proteinase K inhibition (IC = 1.718 ± 0.061 μM), comparable to the standard acarbose (IC = 1.063 ± 0.013 μM) and phenyl methyl sulfonyl fluoride (IC = 0.119 ± 0.014 μM). The unsubstituted compound (4a) emerged as the most potent antifungal agent (17 mm zone of inhibition), outperforming the positive control Terbinafine (zone of inhibition 16 mm). These compounds (4a-j) also displayed moderate antibacterial activity. SAR analysis revealed the influences of various substitutions on the acyl thiourea scaffold. Computational studies, including DFT, molecular docking, and ADMET predictions, supported the biological findings and identified these compounds as promising inhibitors of α-amylase, proteinase K, and microbial pathogens.
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http://dx.doi.org/10.1016/j.abb.2025.110304 | DOI Listing |
Arch Biochem Biophys
January 2025
Department of Biosciences Grand Asian University of Sialkot, Pakistan.
Acyl thiourea scaffolds are frequently employed in drug development to discern unique and essential therapies for the eradication of the most challenging diseases. Hence, we developed a library of novel cyclopropyl incorporating acyl thiourea derivatives (4a-j) and evaluated their antimicrobial, α-amylase, and proteinase K inhibition potential. Compound (4h) (4-methoxy) demonstrated the strongest α-amylase inhibition (IC = 1.
View Article and Find Full Text PDFRSC Adv
November 2024
Departamento de Química Inorgánica, Facultad de Ciencias Químicas, UCM E-28040 Madrid Spain.
The present study reports some fascinating results of Hantzsch's [3 + 2] cyclic condensation of α-bromo-1,3-diketones, a tri-electrophilic synthon generated by bromination of 1,3-diketones using the mild brominating reagent NBS with trinucleophilic -substituted thioureas. Interestingly, out of a total of 20 combinations, 10 resulted in the exclusive formation of the desired 2-(-arylamino)-5-acyl-4-methylthiazoles regioselectively, seven led to the formation of unexpected 2-(-acylimino)-3--aryl-4-methylthiazoles through an interesting C-N acyl migration, and three furnished a mixture consisting of both products. The regioselectivity pattern of the two products may be attributed to a greater electrophilicity of the carbonyl carbon of the acetyl group than that of the acyl group towards both nitrogens of thiourea.
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October 2024
Department of Chemistry, Faculty of Science, Islamic University of Madinah Madinah 42351 Saudi Arabia
To discover promising therapeutic agents, novel diaryl pyrimidine linked acyl thiourea derivatives (6a-j) were designed and synthesized straightforward and multistep synthesis. The structure of these derivatives (6a-j) was confirmed by FTIR, H, and C NMR spectroscopic techniques. The biological screening of these compounds was carried out to assess their bacterial, α-amylase, and proteinase K inhibition potential.
View Article and Find Full Text PDFMini Rev Med Chem
September 2024
Guru Gobind Singh College of Pharmacy, Yamuna Nagar, 135001, Haryana, India.
This review article delves into the critical role of Enoyl acyl carrier protein Reductase (InhA; ENR), a vital enzyme in the NADH-dependent acyl carrier protein reductase family, emphasizing its significance in fatty acid synthesis and, more specifically, the biosynthesis of mycolic acid. The primary objective of this literature review is to elucidate diverse scaffolds and their developmental progression targeting InhA inhibition, thereby disrupting mycolic acid biosynthesis. Various scaffolds, including thiourea, piperazine, thiadiazole, triazole, quinazoline, benzamide, rhodanine, benzoxazole, and pyridine, have been systematically explored for their potential as InhA inhibitors.
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December 2024
CEQUINOR (UNLP-CONICET, CCT-La Plata), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Boulevard 120 e/ 60 y 64 N° 1465 La Plata, B1900, Buenos Aires, Argentina.
The 1-acyl thiourea family [RC(O)NHC(S)NRR] exhibits the flexibility to incorporate a wide variety of substituents into their structure. The structural attributes of these compounds are intricately tied to the type and extent of substitution. In the case of 3-mono-substituted thioureas (R=H), the conformational behavior is predominantly shaped by the presence of an intramolecular N-H ⋅ ⋅ ⋅ O=C hydrogen bond.
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