Multi-target bioactive M(II) pyridine-diamine complexes: synthesis, characterization, in vitro and in silico evaluation.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Multi-target bioactive M(II) pyridine-diamine complexes: synthesis, characterization, in vitro and in silico evaluation.
Συγγραφείς: Nayab S; Department of Chemistry, Shaheed Benazir Bhutto University (SBBU), Sheringal Upper Dir 18050, Khyber Pakhtunkhwa, Islamic Republic of Pakistan., Subhan A; Department of Chemistry, Shaheed Benazir Bhutto University (SBBU), Sheringal Upper Dir 18050, Khyber Pakhtunkhwa, Islamic Republic of Pakistan., Khan SW; Department of Chemistry, Rawalpindi Women University, 6th Road, Satellite Town, Rawalpindi, Punjab, Islamic Republic of Pakistan., Kim D; KNU G-LAMP Research Center, KNU Institute of Basic Sciences, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 41566, Republic of Korea., Yoon M; Department of Chemistry and Green-Nano Materials Research Center, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 41566, Republic of Korea., Jeong SA; Department of Chemistry and Green-Nano Materials Research Center, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 41566, Republic of Korea., Lee H; Department of Chemistry and Green-Nano Materials Research Center, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 41566, Republic of Korea. Electronic address: hyosunlee@knu.ac.kr., Rashid HU; Center for Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas, Pelotas, RS, Brazil; Department of Chemistry, Federal University of Juiz de Fora, Campus Universitário, Rua José Lourenço Kelmer - São Pedro, Juiz de Fora, MG, Brazil. Electronic address: haroongold@gmail.com.
Πηγή: Bioorganic chemistry [Bioorg Chem] 2026 Jul 05; Vol. 175, pp. 109808. Date of Electronic Publication: 2026 Mar 30.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE
Imprint Name(s): Publication: Amsterdam : Elsevier
Original Publication: New York, London, Academic Press.
Ιατρικοί όροι (MeSH): Urease*/antagonists & inhibitors , Urease*/metabolism , Pyridines*/chemistry , Pyridines*/pharmacology , Enzyme Inhibitors*/pharmacology , Enzyme Inhibitors*/chemical synthesis , Enzyme Inhibitors*/chemistry , Coordination Complexes*/pharmacology , Coordination Complexes*/chemistry , Coordination Complexes*/chemical synthesis , Antioxidants*/pharmacology , Antioxidants*/chemistry , Antioxidants*/chemical synthesis , Hypoglycemic Agents*/pharmacology , Hypoglycemic Agents*/chemical synthesis , Hypoglycemic Agents*/chemistry, Canavalia/enzymology ; Bacillus/enzymology ; Bacillus/drug effects ; Molecular Structure ; Structure-Activity Relationship ; Molecular Docking Simulation ; Dose-Response Relationship, Drug ; Humans ; Sporosarcina
Περίληψη: In this study, we synthesized Co(II), Zn(II), and Cd(II) complexes based on a pyridine-derived ligand (N1,N1-diethyl-N2-(pyridin-2-ylmethyl)ethane-1,2-diamine, DEP-R). Single-crystal X-ray diffraction analysis confirmed that all complexes possessed distorted trigonal bipyramidal geometries. The complexes exhibited significant potential against both Jack bean (JB) and Bacillus pasteurii (BP) ureases. Notably, the [Cd(DEP-R)Br2] complex exhibited considerable inhibitory potency against urease (IC50 = 4.51 ± 0.13and 5.71 ± 0.14μM for JB and BP, respectively), outperforming the standard inhibitor Thiourea (IC50 = 11.0 ± 0.62 and 9.10 ± 0.73μM, respectively). In antioxidant assays, [Co(DEP-R)Cl2] displayed the highest DPPH radical scavenging activity. Additionally, all metal complexes showed a superior in vitro anti-diabetic activity compared to both the standard drug and the uncomplexed DEP-R ligand. Molecular docking results showed that [Cd(DEP-R)Br2] and [Co(DEP-R)Cl2] formed multiple favorable interactions (hydrogen bonding, ionic, and π interactions) with the active sites of urease, Leishmania major oxidoreductase, and human pancreatic α-amylase, supporting their promising in vitro activity. ADMET analysis predicted high GI absorption, Lipinski compliance, moderate solubility, good bioavailability, and low cardiotoxicity, with some neurological and respiratory toxicity risks. DFT-based HOMO-LUMO analysis confirmed the stability and reactivity of the complexes. Overall, the present compounds are promising multi-target metallodrug scaffolds.
(Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Antioxidant potential; Metallo-drug scaffold; Pyridine-derived ligand; Urease inhibition; X-ray structures; α-Amylase potential
Substance Nomenclature: EC 3.5.1.5 (Urease)
0 (Pyridines)
0 (Enzyme Inhibitors)
0 (Coordination Complexes)
0 (Antioxidants)
NH9L3PP67S (pyridine)
0 (Hypoglycemic Agents)
SCR Organism: Sporosarcina pasteurii
Entry Date(s): Date Created: 20260405 Date Completed: 20260714 Latest Revision: 20260714
Update Code: 20260715
DOI: 10.1016/j.bioorg.2026.109808
PMID: 41935403
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1090-2120
DOI:10.1016/j.bioorg.2026.109808