Synthesis, Spectroscopic Analysis, Molecular Docking, Molecular Dynamics Simulation of 5-(Adamantan-1-yl)-4-(3-Chlorophenyl)-2,4-Dihydro-3
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            -1,2,4-Triazole-3-Thione, a Potential Anti-proliferative Agent

Abdelrazeq, Alaa S; Ghabbour, Hazem A.; Al-Wahaibi, Lamya H.; Abdelbaky, Mohammed S. M.; Garcı́a-Granda, Santiago; El‐Emam, Ali A.; Pathak, Shilendra K.; Srivastava, Ruchi; Maurya, Anushree; Shukla, Vikas; Prasad, Onkar; Sinha, Leena

doi:10.1080/10406638.2023.2219362

Cited by 1 publication

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“…Derivatives of adamantane, well recognized for their anticancer, − antiviral, − and antibacterial properties, − have also been a focal point of attention for their potential anti-inflammatory properties among medicinal chemists. − Adamantane derivatives have been developed as anti-inflammatory agents consisting of two lipophilic center-linked oxime ethers, oxime esters, amides, and symmetric alcohol bridges . Several adamantane compounds of thiazolyl- N -substituted amides were synthesized and evaluated for their anti-inflammatory-, lipoxygenase-, and cyclooxygenase-inhibiting properties by Kouatly et al The proposition that the substitution of an adamantyl ring for a phenyl ring could lead to opportunities in medicinal chemistry has been made by Fresno et al, documenting the synthesis of adamantyl counterparts of paracetamol that exhibited significant analgesic properties.…”

Section: Introductionmentioning

confidence: 99%

Structural Characterization, Spectroscopic Profile, Molecular Docking, ADMET Properties, Molecular Dynamics Simulation Studies, and Molecular Mechanics Generalized Born Surface Area Analysis of 5-(Adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as a Potential COX Inhibitor

Al-Wahaibi,

El-Emam,

S. M. Abdelbaky

et al. 2024

ACS Omega

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Employing a synergistic combination of theoretical density functional theory (DFT) and experimental techniques, we conducted a comprehensive analysis elucidating the structural and pharmacological attributes of 5-(adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (5A4BT) as a potent COX inhibitor. The X-ray crystallographic data of 5A4BT showed the pivotal role played by weak interactions, notably π−π and C−H−π interactions, alongside hydrogen bonding, in orchestrating the intricate supramolecular architectures within the crystalline lattice. A quantitative analysis of the arrangement of the crystal structure, as well as both inter-and intramolecular interactions, was conducted using Hirshfeld surfaces and 2D fingerprint plots. Additionally, a comprehensive examination of the IR spectra was undertaken, employing both experimental methods and theoretical DFT techniques, to elucidate the vibrational characteristics of the compound. The strength of intermolecular N−H•••S hydrogen bonding and charge transfer within the system was assessed through natural bonding orbital analysis. Moreover, Bader's atoms in molecules theory was employed to estimate the strength of intermolecular hydrogen bonds, revealing strong interactions within the 5A4BT dimer. The title compound exhibited binding affinities of −6.4 and −6.5 kcal/mol for COX1 (PDB 3KK6) and COX2 (1CX2) target proteins, respectively. For the first time, predictions regarding ADMET properties, drug-likeness, and toxicity, including favorable bioavailability, along with 100 ns molecular dynamics simulations, binding free energy, and energy decomposition per residue in the binding cavity of the protein from molecular mechanics generalized born surface area approach, collectively indicate the potential of 5A4BT as a nonselective COX inhibitor.

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