ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Synthesis of trimethoxy-benzylidene-hydrazine-carboxamide compounds: antioxidant, antimicrobial and antiparasitic agent, evaluation of the interaction with BSA and ADMET parameters

Maria José Cristiane da Silva, Diego Santa Clara Marques, Pedro Henrique do Bomfim Nascimento, Raudiney Frankilin Vasconcelos Mendes, Maria Daniela Silva Buonafina-Paz, Dijanah Cota Machado, Fábio André Brayner dos Santos, Luiz Carlos Alves, Rafael Matos Ximenes, Rejane Pereira Neves, Iranildo José da Cruz Filho, and Maria do Carmo Alves de Lima

Laboratory of Chemistry and Therapeutic Innovation, Department of Antibiotics, Federal of Pernambuco, Recife, Brazil

E-mail: iranildoj@gmail.com

Received: 22 August 2023  Accepted: 12 November 2023

Abstract:

The search for new compounds that present low toxicity and high efficiency in the treatment of different diseases is a challenge. Therefore, this study brings as a novelty the synthesis, biological evaluation and a study of the mechanism of action in serum albumin of trimethoxy-benzylidene-hydrazine-carbothioamide compounds. The in silico results received that all compounds showed good oral availability and could be accepted as potential drug candidates. In cytotoxicity assays, the compounds promoted moderate to low toxicity against macrophage cells (82.90 ± 1.19 to 231.49 ± 1.96 µM) and Hepg2 (91.19 ± 1.09 to 254.64 ± 3.96 µM). In addition to not being hemolytic (< 10%). Regarding in vivo toxicity, they were not toxic in mice at a concentration of 2000 mg/kg (gavage). In in vitro biological assays, the compounds showed low antioxidant activity. The antifungal activity assays showed that the compounds were capable of inhibiting the growth of different strains of yeast. The compounds were also able to inhibit the growth of the parasite L. amazonensis in different promastigote (27.84–40.52 µM) and amastigote (29–49.71 µM) forms. Furthermore, they inhibited the growth of T.cruzi trypomastigotes (28.90–45.24 µM). Assays with albumin generally pleased that the compounds can be transported by these proteins without changes in the macromolecules. In this context, we can conclude that the compounds considered can promote different activities and can contribute to the arsenal of new drug candidate compounds that can act as new antifungal and antiparasitic agents.

Keywords: Antifungal agents; Antiparasitic; Albumin

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-023-03214-3

Chemical Papers 78 (3) 1897–1913 (2024)