Abstract

INNOVATIVE COMPUTATIONAL STRATEGIES FOR TROPANE ALKALOID DESIGN: A HOLISTIC PERSPECTIVE

Vani V., Rachel Mathew, Rushda Shajahan* and Navya Anil

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Abstract

This study explores natural products, focusing on alkaloids—especially tropane alkaloids like atropine. It details their classification, biosynthesis, pharmacological significance, isolation, identification, and structural elucidation. Atropine’s chemistry, therapeutic uses, and potential enhancements via complexation and computational tools highlight its importance in drug development and natural product research. The present study focuses on the in silico design and evaluation of ten novel analogues of Atropine to enhance its pharmacological potential. Various computational tools were utilized for analogue generation, structure drawing, and comprehensive profiling. QSAR Toolbox was used to identify structurally similar analogues, while ChemSketch aided in drawing their 2D structures. Molinspiration assessed drug-likeness via Lipinski's Rule of Five, indicating all analogues had favorable properties. PASS predicted strong spasmolytic and antiparkinsonian activities. ADMETlab 3.0 evaluated absorption, distribution, metabolism, and excretion profiles, showing optimal permeability, volume of distribution, and moderate plasma clearance. None of the analogues inhibited CYP1A2, suggesting low drug-drug interaction risk. Toxicity profiles predicted via ProTox 3.0 showed all compounds to be non-hepatotoxic, nonmutagenic, and non-carcinogenic, with good blood-brain barrier permeability. Overall, the designed analogues exhibited promising pharmacokinetic and safety profiles, supporting their potential as viable therapeutic candidates for further experimental validation.

Keywords: Natural products, Tropane alkaloid, Atropine, Analogues.