Synthesis and Evaluation of 2-Hydroxy-1,4-naphthoquinone Derivatives as Potent Antimalarial Agents

Abstract

A series of 3-substituted-2-hydroxy-1,4-naphthoquinone derivatives with a variety of side chains were successfully synthesized by Mannich reaction of 2-hydroxy-1,4-naphthoquinone (lawsone) with selected amines and aldehydes. All substances (1-16) were evaluated for in-vitro antimalarial activity against strains of Plasmodium falciparum by microculture radioisotope technique. Bioassay data revealed that ten derivatives (1-8,11 and 13) displayed significantly good activity with values of IC 50 ranging from 0.77 to 4.05 g/mL. The best biological profile (IC 50 = 0.77 g/mL) was observed in compound 1, possessing a n-butyl substituted aminomethyl group. Experimental results support the potential use of our active Mannich components as promising antimalarial agents in the fight against malaria infections and multidrug resistance problems.

Evaluation of Selectivity Index and Phytoconstituents Profile of Various Extracts from the Stem of Strychnos lucida R. Br. as Anti-malarial

“…Bisindol compounds from the genus Strychnos; isosungucine, hydroxyisosungucine, and strychnogucine B, showed anti-malarial activity against Plasmodium falciparum W2-chloroquine resistance with IC 50 168; 85; 85 nM, respectively. [23] Strychnogucine B inhibited the growth of Plasmodium berghei in murine models by 36% on day 5 and 60% on day 7. [24] The indole alkaloid reserpine, isolated from Corynanthe pachyceras, inhibited the growth of Plasmodium falciparum-chloroquine resistance with IC 50 8.1 μM.…”

The Relevance and Insights on 1,4-Naphthoquinones as Antimicrobial and Antitumoral Molecules: A Systematic Review

“…Lawsone Mannich bases are 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone compounds with important biological activities such as antiparasitic, antibacterial, anticancer, and antiviral, which have a particular interest in medicinal chemistry because the Mannich reaction forms a C-C bond with nitrogencontaining derivatives. This section presents molecules with promissory activity, as shown in Table 1 [31,[42][43][44][45][90][91][92]. showed MICs of 49.7 µ g mL −1 against S. aureus and 24.7 µ g mL −1 against E. coli by 63*.…”

LC-MS Chemical Profiling, In Silico Docking Studies to Unravel the Therapeutic Potential of Streptomyces hygroscopicus as a Source of Antimalarial Bioactive Compounds

“…1,2 This parasite causes malaria infections that can lead to several life-threatening complications. 3 In 2019, approximately 229 million malaria cases were reported in 87 endemic countries, along with records of 409,000 deaths. 4 In Indonesia, the Annual Parasite Incidence (API) increased from 1.12 to 1.61 per 1,000 people in 2022 compared to 2021.…”