Therapeutic Potential of Indole Derivatives as Anti-HIV Agents: A Mini-review

Abstract

: Acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), is one of the leading causes of human deaths. The advent of different anti-HIV drugs over different disease progress has made AIDS/HIV from a deadly infection to chronic and manageable disease. However, the development of multidrug-resistant viruses, together with the severe side effects of anti-HIV agents, compromised their efficacy and limited the treatment options. Indoles, the most common frameworks in the bioactive molecules, represent attractive scaffolds for the design and development of novel drugs. Indole derivatives are potential inhibitors of HIV enzymes such as reverse transcriptase, integrase and protease, and some indole-based agents like Delavirdine have already been applied in clinics or under clinical evaluations for the treatment of AIDS/HIV, revealing that indole moiety is a useful template for the development of anti-HIV agents. This review focuses on the recent advancement of indole derivatives including indole alkaloids, hybrids, and dimers with anti-HIV potential, covering articles published between 2010 and 2020. The chemical structures, structure-activity relationship and mechanisms of action are also discussed.

Voacanga globosa Spirobisindole Alkaloids Exert Antiviral Activity in HIV Latently Infected Cell Lines by Targeting the NF-κB Cascade: In Vitro and In Silico Investigations

“…Based on the data, globospiramine ( 1 ) and vobtusine lactone ( 3 ) showed inhibitory activity on HIV production, with a therapeutic index (2.7 to 3.18) where a value of > is the safety numerical value ( Figure 2 , Table 2 ). This finding corroborates further on previous studies on indole alkaloids showing inhibitory activity on HIV [ 43 ] such as the Iboga type of indole plant alkaloid reduced viral production in macrophages in vitro and inhibited HIV reverse transcriptase [ 44 ], trigonoliimine A with moderate anti-HIV activity [ 45 ] and analogs of natural pimprinine alkaloid, an inhibitor of HIV integrase [ 46 ] to name a few. We observed also that deoxyvobtusine ( 2 ) did not demonstrate significant inhibitory activity on HIV production from TNF-α stimulated OM10.1 cells, but exhibited a remarkable therapeutic index value in TNF-α stimulated J-Lat cells.…”

Divergent Strategy for the Synthesis of Indolopyrazines Fused to Benzopyrimidinones and Benzimidazoles: Identification of Antiproliferative Molecules

“…[1b,2-4,6,8] Representative examples of indole-based drugs are enlisted in Figure 1. [4,9] Indoles are characterized by their ability to form hydrogen bonds through the nitrogen which made them promising adenosine triphosphate (ATP)-competitive kinase inhibitors. [10] Also, the existence of low-lying CÀ N σ* orbitals, along with small areas of reduced electron density located on the nitrogen atom, play a major role in enhancing drug-target interactions, which improve the binding affinity towards biological targets.…”

“…Nitrogen heteroaromatic fused bicyclic ring systems such as Indoles, constituted the core scaffold of a wide variety of biologically important molecules, including anti‐cancer, [3] anti‐viral, [4] anti‐bacterial, [5] immunomodulatory, [6] anti‐psychotic, [7] and anti‐inflammatory [5a] agents among others [1b,2–4,6,8] . Representative examples of indole‐based drugs are enlisted in Figure 1 [4,9] .…”

“…Nitrogen heteroaromatic fused bicyclic ring systems such as Indoles, constituted the core scaffold of a wide variety of biologically important molecules, including anti‐cancer, [3] anti‐viral, [4] anti‐bacterial, [5] immunomodulatory, [6] anti‐psychotic, [7] and anti‐inflammatory [5a] agents among others [1b,2–4,6,8] . Representative examples of indole‐based drugs are enlisted in Figure 1 [4,9] . Indoles are characterized by their ability to form hydrogen bonds through the nitrogen which made them promising adenosine triphosphate (ATP)‐competitive kinase inhibitors [10] .…”

A new exploration toward adamantane derivatives as potential anti‐MDR agents: Design, synthesis, antimicrobial, and radiosterilization activity as potential topoisomerase IV and DNA gyrase inhibitors

“…The versatility of isatin's molecular structure makes it an ideal platform for structural modification and derivatization, as evidenced by the fact that many isatin derivatives exhibit a broad range of biological activities such as anticonvulsant (Fayed, Ragab, et al, 2021), antimicrobial (M. A. Salem, Ragab, Askar, et al, 2020; M. A. Salem, Ragab, El‐Khalafawy, et al, 2020), antidepressant (Hamid et al, 2017), anti‐inflammatory (A. Z. Salem et al, 2021), anticancer (Ammar et al, 2018), and anti‐HIV (Chen et al, 2021).…”