Endoperoxide-8-aminoquinoline hybrids as dual-stage antimalarial agents with enhanced metabolic stability was written by Capela, Rita;Magalhaes, Joana;Miranda, Daniela;Machado, Marta;Sanches-Vaz, Margarida;Albuquerque, Ines S.;Sharma, Moni;Gut, Jiri;Rosenthal, Philip J.;Frade, Raquel;Perry, Maria J.;Moreira, Rui;Prudencio, Miguel;Lopes, Francisca. And the article was included in European Journal of Medicinal Chemistry in 2018.Formula: C13H14BrNO2 This article mentions the following:
A library of 1,2,4,5-tetraoxane-8-aminoquinoline hybrids, I [R = Ph, 3-furyl, 4-F3CC6H4, etc.; X = CH(Me), CH2, (CH2)2; Y = CO, CH2] with the metabolically labile C-5 position of the 8-aminoquinoline moiety blocked with aryl groups, was synthesized and screened for antiplasmodial activity and metabolic stability. The hybrid compounds inhibited development of intra-erythrocytic forms of the multidrug-resistant Plasmodium falciparum W2 strain, with EC50 values in the nM range, and with low cytotoxicity against mammalian cells. The compounds also inhibited the development of P. berghei liver stage parasites, with the most potent compounds displaying EC50 values in the low μM range. SAR anal. revealed that unbranched linkers between the endoperoxide and 8-aminoquinoline pharmacophores are most beneficial for dual antiplasmodial activity. Importantly, hybrids were significantly more potent than a 1:1 mixture of 8-aminoquinoline-tetraoxane, highlighting the superiority of the hybrid approach over the combination therapy. Furthermore, aryl substituents at C-5 of the 8-aminoquinoline moiety improve the compound’s metabolic stability when compared with their primaquine (i.e. C-5 unsubstituted) counterparts. Overall, this study revealed that blocking the quinoline C-5 position does not resulted in loss of dual-stage antimalarial activity, and that tetraoxane-8-aminoquinoline hybrids were an attractive approach to achieve elimination of exo- and intraerythrocytic parasites, thus with the potential to be used in malaria eradication campaigns. In the experiment, the researchers used many compounds, for example, N-(5-Bromopentyl)phthalimide (cas: 954-81-4Formula: C13H14BrNO2).
N-(5-Bromopentyl)phthalimide (cas: 954-81-4) belongs to organobromine compounds. A variety of minor organobromine compounds are found in nature, but none are biosynthesized or required by mammals. Organobromine compounds have fallen under increased scrutiny for their environmental impact. The principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.Formula: C13H14BrNO2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary