1. Structure-based design, synthesis, biological evaluation, and molecular docking of novel 10-methoxy dibenzo[b,h][1,6]naphthyridinecarboxamides
- Author
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D. Sunny, Balaraman Selvakumar, S. Madhuri, K.N. Vennila, Kuppannagounder P. Elango, and V. Satish
- Subjects
chemistry.chemical_classification ,biology ,010405 organic chemistry ,Stereochemistry ,Drug discovery ,Carboxylic acid ,In silico ,Organic Chemistry ,Active site ,01 natural sciences ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Design synthesis ,chemistry ,biology.protein ,Bioorganic chemistry ,Structure based ,General Pharmacology, Toxicology and Pharmaceutics ,Biological evaluation - Abstract
10-methoxy dibenzo[b,h][1,6]naphthyridine carboxylic acid was successfully synthesized from 3-methoxyaniline by a new route. By utilizing a structure-based epharmacophore developed from the active site of 3-phosphoinositide-dependent kinase-1, a series of nine novel 10-methoxy dibenzo[b,h][1,6]naphthyridinecarboxamides was synthesized and characterized by different spectral techniques. Three of them are found to be active by screening against A549 cell line and showed significant anticancer activity when compared to a marketed lung cancer drug, pemetrexed. The molecular docking and in silico pharmacokinetic predictions provide detailed understanding for utilizing the dibenzo[b,h][1,6]naphthyridine scaffold in future drug discovery and development of PDK1 inhibitors.
- Published
- 2020