A minimalistic approach to develop new anti-apicomplexa polyamines analogs

Abstract

The development of new chemical entities against the major diseases caused by parasites is highly desired. A library of thirty diamines analogs following a minimalist approach and supported by chemoinformatics tools have been prepared and evaluated against apicomplexan parasites. Different member of the series of N,N′−disubstituted aliphatic diamines shown in vitro activities at submicromolar concentrations and high levels of selectivity against Toxoplasma gondii and in chloroquine-sensitive and resistant-strains of Plasmodium falciparum. In order to demonstrate the importance of the secondary amines, ten N,N,N′,N′−tetrasubstituted aliphatic diamines derivatives were synthesized being considerably less active than their disubstituted counterpart. Theoretical studies were performed to establish the electronic factors that govern the activity of the compounds.

Establishment of Babesia bovis In Vitro Culture Using Medium Free of Animal Products

“…One of these is putrescine; previous studies have confirmed that it is a key component that allows the rapid growth of Babesia spp. and other Apicomplexa parasites [ 1 , 11 , 36 ]. This is further supported by in silico analysis of the B. bovis genome that has shown the parasite cannot biosynthesize polyamines [ 37 ].…”

“…The phylum Apicomplexa comprises intracellular protozoan parasites of enormous global importance in the medical and veterinary fields [ 1 ]. Babesia bovis and B. bigemina are obligate intraerythrocytic parasites that cause bovine babesiosis in tropical and subtropical regions [ 2 , 3 ], and both parasites are transmitted by Rhipicephalus microplus or R. annulatus .…”

Expanding the scope of novel 1,2,3-triazole derivatives as new antiparasitic drug candidates

“…The standard antimalarial agent chloroquine and artemisinin were used as the positive controls and DMSO as negative control. 56,57…”

“…The standard antimalarial agent chloroquine and artemisinin were used as the positive controls and DMSO as negative control. 56,57 In vitro activity against L. donovani (IC 50 ). Leishmania donovani promastigotes of the S1 Sudan strain (2 × 10 6 cell per mL) were cultured at 26 °C in polystyrene cell-culture flasks (25 cm 2 ), containing RPMI-1640 medium (without sodium bicarbonate and sodium pyruvate) with 10% FBS.…”

A gram-scale synthesis of a macrocyclic amidinourea with strong antifungal activity through a Fukuyama tri-protected polyamine intermediate

“…Hence, many scientists devoted part of their work to the analysis of protecting group strategies, as testified by the remarkable work done in late 1990s/early 2000s by Fukuyama and co-workers, [8][9][10][11][12] as well as by many others. [13][14][15][16][17][18][19][20][21][22][23] In the last years, our research group focused its efforts on the preparation of a series of compounds bearing interesting antifungal properties, as we reported in previous works, [24][25][26][27][28][29][30][31][32] well represented by compound 1 (Figure 1). These compounds showed good activities against various Candida strains, most notably albicans, guillermondii, kefyr, glabrata.…”