Conducting 2D and 3D QSAR Analyses and Molecular Docking Studies of
Analogues of 2-(1-(1,3,4-thiadiazol-2-yl)piperidin-4-yl)ethan-1-ol with the
Aim of Identifying Promising Drug Candidates for Targeting Glioblastoma

Meichen      Pan; Lingxue      Cheng; Yiguo      Wang; Chunyi      Lyu; Chao      Hou; Qiming      Zhang

doi:10.2174/1570180820666230901162718

Abstract

Background: 2-(1-(1,3,4-thiadiazol-2-yl)piperidin-4-yl) ethan-1-ol analogues represent novel glutaminase 1 inhibitors. Their exemplary antineoplastic efficacy underscores their prospective utility in glioblastoma chemotherapy.

Objective: This study aimed to elucidate 2D and 3D-QSAR models that authenticate the antineoplastic efficacy of ethan-1-ol analogues and delineate optimal structural configurations conducive to new pharmaceutical design.

Methods: The Heuristic Method (HM) was employed for the development of a 2D-linear QSAR paradigm, whilst the Gene Expression Programming (GEP) algorithm was employed for a 2D-nonlinear QSAR paradigm. Concurrently, the CoMSIA methodology was deployed to scrutinize the nexus between pharmaceutical structure and potency. An ensemble of 200 nascent anti-glioma ethan-1-ol compounds was conceptualized, and their potency levels were prognosticated via chemical descriptors and molecular field delineations. Pharmaceuticals epitomizing peak potency were earmarked for molecular docking validation.

Results: The empirical modeling exhibited pronounced superiority with the 3D paradigm, succeeded by the GEP nonlinear paradigm and culminated with the HM linear model. The 3D paradigm was characterized by a robust Q2 (0.533), R2 (0.921), and F-values (132.338) complemented by a minimal SEE (0.110). The molecular descriptor MNO coupled with the hydrogen bond donor field facilitated novel pharmaceutical conceptualizations, leading to the identification of the quintessential active molecule, 24J.138, lauded for its superlative antineoplastic attributes and docking proficiency.

Conclusion: The orchestration of bidimensional and tridimensional paradigms, synergized by innovative amalgamation of contour maps and molecular descriptors, provides novel insights and methodologies for the synthesis of glioblastoma chemotherapeutic agents.

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DOI https://dx.doi.org/10.2174/1570180820666230901162718	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X

Letters in Drug Design & Discovery

Conducting 2D and 3D QSAR Analyses and Molecular Docking Studies of Analogues of 2-(1-(1,3,4-thiadiazol-2-yl)piperidin-4-yl)ethan-1-ol with the Aim of Identifying Promising Drug Candidates for Targeting Glioblastoma

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