Applications of medicinal chemistry for drug discovery against Acanthamoeba infections

Abstract

Acanthamoeba is a genus of free‐living amoebae, pervasively found in the environment. Most of its pathogenic species are the causative agent of sight‐threatening Acanthamoeba keratitis and fatal granulomatous amoebic encephalitis. Despite the advancements in the field of chemotherapy, treating Acanthamoeba infections is still challenging due to incomplete knowledge of the complicated pathophysiology. In case of infection, the treatment regimen for the patients is often ineffective due to delayed diagnosis, poor specificity, and side‐effects. Besides the resistance of Acanthamoeba cysts to most of the drugs, the recurrence of infection further complicates the recovery. Thus, it is necessary to develop an effective treatment which can eradicate these rare, but serious infections. Based on various computational and in vitro studies, it has been established that the synthetic scaffolds such as heterocyclic compounds may act as potential drug leads for the development of antiamoebic drugs. In this review, we report different classes of synthetic compounds especially heterocyclic compounds which have shown promising results against Acanthamoeba. Moreover, the antiamoebic activities of synthetic compounds with their possible mode of actions against Acanthamoeba, have been summarized and discussed in this review.

Gongolarones as antiamoeboid chemical scaffold

“…Recently, the incidence of AK cases has shown a remarkable increase worldwide which is mainly related to the increase of contact lens wearers [9]. In addition, the treatment of these infections has been undermined by resistance, variable efficacy between strains or species, toxicity, parenteral administration, requirement for long courses of administration and adverse effects and cost [10,11].…”

Natural Terpenes Inhibit the Cytopathogenicity of Naegleria fowleri Causing Primary Amoebic Meningoencephalitis in the Human Cell Line Model

“…Toxicology assessment is crucial to determine the safe dose required for effectiveness and to assess any adverse effects. 56 In the present study, we used three cell lines, HaCaT, HeLa, and neuroblastoma (SH-SY5Y), to assess the toxicity of the tested compounds. As we know, Naegleria enters the body through the nose, and keratinocytes act as a barrier for N. fowleri.…”

Synthesis, Characterization and Biological Properties of Mn (II) and Cu (II) Complexes with Sulfonamide and Imidazole Derivatives: Genotoxicity, ADME Profile, and Molecular Docking Studies**

“…Consequently, the search for novel and effective candidates for amoebicidal drugs is imperative in amoebiasis therapy. [14][15][16] On the other hand, the last COVID 19 pandemic caused by the SARS-CoV-2 virus was affected all populations and was rapidly spread. [17] This later requires a new therapy to battle the infectious diseases resulting from SARS-CoV-2 virus.…”

“…Nevertheless, this drug is associated with frequent adverse effects including nausea, vomiting, headache, metallic taste, glossitis, and, in rare instances, convulsions. Consequently, the search for novel and effective candidates for amoebicidal drugs is imperative in amoebiasis therapy [14–16] …”