Synthesis, anti-parasitic activity and QSAR study of a new library of polysubstituted tetrahydronaphtho[1,2-b]azepines

Virtual Screening Based on QSAR and Molecular Docking of Possible Inhibitors Targeting Chagas CYP51

“…Chagas, a tropical disease endemic to Latin America, is caused by the parasite Trypanosoma cruzi (T. cruzi), first described in 1909 [1][2][3]. e most affected population is very low-income people, who do not have the economic resources to pay for expensive treatments and live in conditions of high vulnerability [4][5][6].…”

“…e pharmacological therapy currently used is aimed at preventing the chronicity of the infection since the efficacy of antiparasitic drugs decreases in the chronic phases of the disease. e effectiveness of the treatment in the acute phase has been demonstrated [7], while the chronic stage can take up to 20 years resulting in multiple-organ damage [6][7][8]. Studies show that treatment effectiveness in the acute phase is 50-70%, while in the chronic phase, the effectiveness is reduced to 8-30% [9,10].…”

“…ere is no effective treatment for Chagas disease in all its forms; treatment with nifurtimox and benznidazole is highly toxic [6,7,11]. Both compounds are heterocyclic with a furan and imidazole-nitrogenated ring, respectively, which act by inducing cytotoxicity in the parasite by interacting with the nitroreductase enzymes of the parasites [12][13][14][15].…”

Synthesis of naphtho[1,2‐b]‐, naphtho[2,1‐b]‐, and naphtho[2,3‐b]azepinones via proton‐induced cyclization of N‐1(2)‐naphthyl styrylacetamides

“…In the recent years, the scope of fused 1 Н ‐azepines under study has been significantly extended by inclusion of their naphtho[ b ]‐fused derivatives; some of which act as potent growth hormone secretagogues, γ‐secretase modulators, aldose reductase inhibitors, tranquilizers, anti‐human immunodeficiency virus (HIV) and antiparasitic drugs, and dopamine receptor agonists …”

“…Among the most widely used synthetic routes to naphtho[1,2‐ b ]azepine and naphtho[2,3‐ b ]azepine are the Beckmann rearrangement of the corresponding hydrogenated phenanthrenones and diverse intramolecular catalytic cyclizations of functionalized 1(2)‐aminonaphthalenes . Both approaches quite often suffer from certain limitations such as the need for hardly accessible reagents, multistep syntheses, the lack of selectivity, and low yields.…”