In vitro and in silico DNA interaction studies of a series of 3-carboxamide-4-quinolone derivatives prepared from an one-pot stepwise synthesis (OPSS) method

•An one-pot stepwise method for synthesizing fifteen 3-carboxamide-4-quinolone derivatives, including compounds with previously reported antitumor profile.•Substances were prepared with yields ranging from 35 % to 88 %, resulting in a reduction in the number of synthetic steps and a net saving of so...

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Bibliographic Details
Published in:	Journal of molecular structure Vol. 1321; p. 140064
Main Authors:	do Vale, Thiago Mota, de Oliveira Andrade, Joice Cristina, Cunha, Anna Claudia, Iglesias, Bernardo Almeida, Rodrigues, Bruna Matiuzzi, Chaves, Otávio Augusto, Batalha, Pedro Netto, de Souza, Maria Cecília Bastos Vieira, da Costa Santos Boechat, Fernanda
Format:	Journal Article
Language:	English
Published:	Elsevier B.V 05-02-2025
Subjects:	Amide DNA interactions Molecular docking Oxoquinoline Amide Oxoquinoline DNA interactions Molecular docking
Online Access:	Get full text
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Summary:	•An one-pot stepwise method for synthesizing fifteen 3-carboxamide-4-quinolone derivatives, including compounds with previously reported antitumor profile.•Substances were prepared with yields ranging from 35 % to 88 %, resulting in a reduction in the number of synthetic steps and a net saving of solvents used for workup and purification.•Interaction studies with calf-thymus DNA using spectroscopic and theoretical methods were conducted.•Additional molecular docking in silico studies provided insights into the interaction dynamics between 3-carboxamide-4-quinolone and DNA. The 3-carboxamide-4-quinolone framework is highly regarded in the fields of Medicinal and Bioorganic Chemistry mainly due to its widespread bioactive properties. This versatile scaffold allows for the development of compounds with various pharmacological effects. In this sense, the present work explores a novel one-pot stepwise (OPPS) method for synthesizing fifteen 3-carboxamide-4-quinolone derivatives, some of which exhibit antitumor profiles in previous works. These compounds were synthesized using the OPPS methodology with yields ranging from 35 % to 88 %, streamlining the synthetic process and reducing solvent usage. Furthermore, interaction studies with calf-thymus DNA were done by UV–Vis absorption and steady-state fluorescence measurements combined with molecular docking calculations. Compounds 10a-b, 10d-g, 10k, and 10n were selected for the CT-DNA interaction assays, from which it was possible to demonstrate their DNA-binding property through peripheral secondary interactions. Molecular docking results suggested van der Waals and hydrogen bonds as the main binding forces responsible for the interactive profile between the nucleobases and the 3-carboxamide-4-quinolone derivatives. All these results unveiled promising insights into their role as DNA replication inhibitors, highlighting their potential in developing antiproliferative drugs. [Display omitted]
ISSN:	0022-2860
DOI:	10.1016/j.molstruc.2024.140064