Turkish Journal of Biology
Abstract
Background/aim: Obesity has become a global health crisis with an increasing prevalence, necessitating the search for effective therapies. Schiff base derivatives, known for their broad pharmacological activities, have gained attention as potential antiobesity agents. This study aimed to investigate the lipase inhibitory potential of novel Schiff base derivatives and assess their drug-like properties through in vitro assays and in silico methods. Materials and methods: The lipase inhibitory activity of synthesized Schiff base derivatives was evaluated using in vitro assays, with IC50 values determined for each compound. Additionally, in silico ADMET predictions (absorption, distribution, metabolism, excretion, and toxicity), molecular docking studies, and density functional theory (DFT) calculations were conducted to assess the pharmacokinetic properties and binding potential of the compounds to the lipase active site. Results: The synthesized Schiff base derivatives demonstrated significant lipase inhibitory activity, with IC50 values of 995.74 ± 0.010 μM (6) and 1985.51 ± 0.041 μM (2), comparable to the reference compound quercetin (843.06 ± 0.0007 μM). In silico ADMET analyses revealed that compounds 2 and 6 possess favorable pharmacokinetic properties and exhibit drug-like characteristics. Molecular docking studies showed robust binding interactions between these compounds and the lipase active site, which were further corroborated by DFT calculations that identified reactive regions and stable conformations. Among the compounds, compound 6 exhibited the most effective inhibition and interaction profile, indicating its potential as a lipase inhibitor. These findings underscore the potential of Schiff base derivatives as promising antiobesity agents. Conclusion: The results of our study highlight the potential of Schiff base derivatives as promising candidates for antiobesity therapy, given their significant lipase inhibitory activity and favorable in silico predictions. Further research is needed to elucidate the precise mechanisms of action and assess the efficacy of these compounds in vivo.
Author ORCID Identifier
MADJDA BENGUECHOUA: 0000-0002-9411-330X
MEBARKA IMANE BENGUECHOUA: 0000-0002-7836-8935
KHEDIDJA BENAROUS: 0000-0001-9112-6730
HOUSSEM BOULEBD: 0000-0002-7727-8583
IBTISSEM KADI: 0000-0003-0408-0135
ARİF MERMER: 0000-0002-4789-7180
YAKUP ŞİRİN: 0000-0002-9769-9406
ALAEDDINE KAOUKA: 0000-0002-1118-7603
MOHAMED YOUSFI: 0000-0003-3947-9867
DOI
10.55730/1300-0152.2748
Keywords
Schiff base derivatives, lipase inhibition, in vitro, in silico, ADMET, molecular docking
First Page
324
Last Page
335
Publisher
The Scientific and Technological Research Council of Türkiye (TÜBİTAK)
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
BENGUECHOUA, M, BENGUECHOUA, M, BENAROUS, K, BOULEBD, H, KADI, I, MERMER, A, ŞİRİN, Y, KAOUKA, A, & YOUSFI, M (2025). Discovery and characterization of selective lipase-inhibiting polyheterocyclic derivatives: a combined in silico and in vitro study. Turkish Journal of Biology 49 (3): 324-335. https://doi.org/10.55730/1300-0152.2748
