Author:
Escala Nerea,Pineda Laura M.,Ng Michelle G.,Coronado Lorena M.,Spadafora Carmenza,del Olmo Esther
Abstract
AbstractMalaria cases and deaths keep being excessively high every year. Some inroads gained in the last two decades have been eroded especially due to the surge of resistance to most antimalarials. The search for new molecules that can replace the ones currently in use cannot stop. In this report, the synthesis of benzimidazole derivatives guided by structure–activity parameters is presented. Thirty-six molecules obtained are analyzed according to their activity against P. falciparum HB3 strain based on the type of substituent on rings A and B, their electron donor/withdrawing, as well as their dimension/spatial properties. There is a preference for electron donating groups on ring A, such as Me in position 5, or better, 5, 6-diMe. Ring B must be of the pyridine type such as picolinamide, other modifications are generally not favorable. Two molecules, 1 and 33 displayed antiplasmodial activity in the high nanomolar range against the chloroquine sensitive strain, with selectivity indexes above 10. Activity results of 1, 12 and 16 on a chloroquine resistance strain indicated an activity close to chloroquine for compound 1. Analysis of some of their effect on the parasites seem to suggest that 1 and 33 affect only the parasite and use a route other than interference with hemozoin biocrystallization, the route used by chloroquine and most antimalarials.
Funder
Ministery of Environment: Endowment for Water, Protected Areas and Wildlife, Panama
Sistema Nacional de Investigación, Secretaría Nacional de Ciencia, Tecnología e Innovación
Ministerio de Ciencia e Innovación
Publisher
Springer Science and Business Media LLC
Reference47 articles.
1. Ashley, E. A., Pyae Phyo, A. & Woodrow, C. J. Malaria. Lancet 391(10130), 1608–1621. https://doi.org/10.1016/s0140-6736(18)30324-6 (2018).
2. World Malaria Report. World Health Organization. https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2021 (2021). Accessed 10 December 2022.
3. WHO recommends groundbreaking malaria vaccine for children at risk. https://www.who.int/news/item/06-10-2021-who-recommends-groundbreaking-malaria-vaccine-for-children-at-risk (2021). Accessed 10 December 2022.
4. Olotu, A. et al. Seven-year efficacy of RTS, S/AS01 malaria vaccine among young African children. N. Engl. J. Med. 374, 2519–2529. https://doi.org/10.1056/NEJMoa1515257 (2016).
5. Guideline for Malaria. World Health Organization. https://www.who.int/publications/i/item/guidelines-for-malaria (2021).
Accessed 10 December 2022.
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