Work

DprE1 inhibitors in tuberculosis: integrating structural binding determinants, IC 50 –MIC translation, and physicochemical constraints for rational drug design

Year: 2026

Type: review

Abstract: -MIC disconnect is associated with permeability barriers, intracellular accumulation, efflux, metabolic stability, and pharmacokinetic limitations rather than intrinsic binding affinity alone. Comparative analysis across inhibitor classes reveals that successful compounds are those that balance hydrophobic cavity occupation with controlled lipophilicity and sufficient cellular exposure. Overall, this review provides a medicinal-chemistry framework for understanding the relationship between structural optimization and antibacterial performance and highlights that future progress in DprE1 inhibitor design will depend on integrating molecular recognition with translational efficiency rather than maximizing potency in isolation.

Source: RSC Medicinal Chemistry

DOI: 10.1039/d6md00729e

Authors: Fady H. Fayek, Mai H. A. Mousa, Mona F. Said, Hanan H. Georgey, Nagwa M. Abdel Gawad

Institutions: Egyptian Chinese University, Cairo University

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Drug Discovery

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W7225243702

FWCI:

Cites: 70

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Related to: 10