Phthalimide analogs for antimalarial drug discovery

Abstract

Malaria remains as one of the most life-threatening diseases and thus major public health concern all around the world. The disease becomes devastating if not treated with proper medication on...

Design of N-11-Azaartemisinins Potentially Active against <i>Plasmodium falciparum</i> by Combined Molecular Electrostatic Potential, Ligand-Receptor Interaction and Models Built with Supervised Machine Learning Methods

“…The interactions between N-11-azaartemisinins (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) and heme in their entirety occur preferentially orienting Fe 2+ to heme. The distance d(Fe-O 1 ) is smaller than d(Fe-O 2 ) in all ligand-heme interactions and, in general, d(Fe-O1) has higher values for N-11-azaartemesinins cha, when compared to N-11-azaartemisinins cla.…”

“…The relative activities were obtained with the expression: relative IC 50 = IC 50 (artemisinin)/IC 50 (N-11-azaartemisinin) [51], where IC 50 corresponds to 50% of the inhibitory concentration of the compounds. The following hypothesis was considered in the research: N-11-azaartemisinins with relative IC50 ≥ 0.24 correspond to cha (1-8) and N-11-azaartemisinins with relative IC50 < 0.24 correspond to cla (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

“…About the investigated N-11-azaartemisinis) also exhibit the endoperoxide linkage necessary for antimalarial activity. Figure 3 shows the MEP maps for the N-11-azaartemisinins of the training set obtained by the inclusion of substituents in the N atom of the lactam function (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). As one can see in this figure, the MEP maps are similar to artemisinin and 11-azaartemisinin in the 1, 2, 4 trioxane ring region, with the electron density of some molecules more concentrated in this region, indicating greater biological activity.…”

4-(N-Phthalimido)phenyl Isonitrile as a Novel Convertible Isocyanide Analogue with the Odorless Property as an Extra Bonus

“…The novelty of this work comes from the synthesis of a novel isonitrile containing a phthalimido group (Pht) with plenty of desirable properties such as the presence of a protecting group, a pharmacophore moiety, and odorlessness as an extra bonus. Moreover, Pht-based compounds demonstrate therapeutic and pharmaceutical applications and thus function as leading points for the design of novel drug candidates, showing safe and effective anticancer − and antimicrobial activities. Moreover, the Pht group participates in a vast number of potent anticancer drugs, such as thalidomide 1 , pomalidomide 2 , and lenalidomide 3 , and a strong anticonvulsant and antiepileptic drug, taltrimide 4 (Figure ).…”

Photoinduced desaturative β-C(sp3)–H amidation of N-phenylpiperidine with phthalimide driven by electron donor–acceptor complexes

“…[1][2][3][4][5][6] It has been reported that phthalimide derivatives often exhibit diverse biological activities including antioxidant, 7 antimicrobial, 8 anti-cancer, 9,10 antiinflammatory, 11 antimalarial, etc. 12 For example, thalidomide, a widely used immunomodulatory drug, exhibits the highest in vivo anti-inflammatory activity. 13 With increasing interest in the activation of C-H bonds, several strategies for direct C-H amidation have been developed.…”