Synthesis and antimalarial activity of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives

Abstract

A series of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives has been synthesized and evaluated for antimalarial activity in vitro against the human malaria parasite, Plasmodium falciparum (Vietnam Smith strain, chloroquine-resistant at the R3 level). The most active compounds, 2-aziridinyl-1,4-naphthoquinon-5-yl p-ethylbenzenesulfonate (13), 2-aziridinyl-1,4-naphthoquinon-5-yl p-tert-butylbenzenesulfonate (48), and 2-aziridinyl-5-hydroxy-1,4-naphthoquinone (5) produced 50% inhibition of the growth of P. falciparum at 9.6 x 10(-8), 2.4 x 10(-8), and 8.8 x 10(-8) M, respectively.

Malaria Chemotherapeutics Part I: History of Antimalarial Drug Development, Currently Used Therapeutics, and Drugs in Clinical Development

“…Considerable activity has only been reported for some 2-aziridylnaphthoquinones such as compound 90, which has an IC 50 value of 24 nm. [320] …”

Recent advances in 1,4-benzoquinone chemistry

“…3 Their role as electron transfer agents in primary metabolic processes like photosynthesis and respiration is vital to human life. A large number of chemical derivatives with 1,4-benzoquinone as the basic subunit exhibit prominent pharmacological applications such as antibiotic, 4,5 antitumor, [6][7][8][9] antimalarial, 7,10 antineoplastic, 11 anticoagulant 12 and herbicidal activity. 13 Wide applications of quinones can also be found in the field of synthetic organic chemistry.…”

Electro-organic synthesis of dibenzylaminodioxocyclohexa-dienecarboxylic acids

“…Alkylaminoquinones are of considerable interest because they exhibit antitumor and antimalarial activities 1,2 and many of them are also involved in enzyme inhibition and DNA cross-linking. 3 1,2-Benzoquinone derivatives have been less extensively studied than the 1,4-benzoquinone derivatives because they are more difficult to prepare.…”