Banca de DEFESA: LAMARK CARLOS I

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : LAMARK CARLOS I
DATE: 08/04/2025
TIME: 09:00
LOCAL: VIDEOCONFERÊNCIA
TITLE:

Synthesis, characterization and antimalarial evaluation

of 1H-1,2,3- triazoles-1,4-disubstituted derivatives of melatonin and tryptamine

KEY WORDS:

malaria; Plasmodium Falciparum; indole; melatonin; click chemistry.

PAGES: 239
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

Present in more than 90 countries, malaria is considered one of the most lethal infectious

diseases in the world. Caused by parasites of the Plasmodium genus, it is transmitted by

female Anopheles mosquitoes. The most recent data on the epidemiology of the disease

released by the World Health Organization (WHO) estimate that in 2023 there were

approximately 263 million cases of malaria worldwide, with more than 597,000 deaths. The

search for new compounds with antimalarial activity is urgent, since resistance to the classic

drugs used for treatment has already been described in countries where the disease is endemic.

Melatonin is a hormone with an indole structure and plays a central role in controlling the

replication of the parasite that causes malaria and stabilizing parasitemia. Blocking the

pathway of this hormone may contribute to the discovery of new antimalarial drugs. The aim

of this work was to prepare triazoles derived from the indole nucleus that may exhibit

antimalarial activity on the parasite cell cycle, inhibiting the growth or causing the death of

Plasmodium falciparum. Several novel molecules containing in their structure, heterocyclic

1H-1,2,3-triazole rings and benzene ring with different substituents were designed and

synthesized in this work by means of the CuAAC “click chemistry” reaction catalyzed by

copper (I). In the synthesis step, the melatonin precursor was subjected to the alkylation

reaction to form the respective terminal alkyne intermediate (3). Subsequently, this

intermediate was treated with different prepared aromatic azidocompounds (1a-e) to form the

respective triazole products of the series (4a-e) derived from melatonin with yields ranging

from 68 to 91%. Tryptamine, a congener of melatonin, was also used as a precursor in the

formation of triazole sulfonamide compounds of the series (8a-e) and (11a-e) with yields

ranging from 59.4 to 91%. The structural elucidation of the intermediates and products

obtained was successfully performed using IR and NMR spectroscopic techniques of 13C and

1 H isotopes. Compounds (10), (4d) and (4e) exhibited measurable antimalarial activity with

IC50 values of 33.38 ± 1.487 µM, 31.92 ± 6.370 µM and 11.57 ± 1.863 µM, respectively,

showing low cytotoxicity in mammalian cells. Among these, (4e) emerged as the most potent

and least cytotoxic with SI (>4.32). These results highlight the potential of these three

compounds as promising candidates for further investigation, providing a solid basis for

future studies aiming at their optimization and development as antimalarial agents.

COMMITTEE MEMBERS:
Presidente - 1571756 - ALESSANDRO KAPPEL JORDAO
Externo ao Programa - 1803692 - FABRICIO GAVA MENEZES - nullExterno à Instituição - THALES ALLYRIO ARAUJO DE MEDEIROS FERNANDES - UERN