Efforts to control HIV/AIDS since the late 1980 s have resulted in a global decline in new infections and deaths (De Clercq, 2009), aligning with the 2030 goal to end AIDS (Zhan P et al., 2009). Treatment has prevented approximately 20.8 million deaths, but in 2022, 9.2 million people with HIV lacked treatment, and 2.1 million treated individuals did not achieve viral suppression, making AIDS the fourth-leading cause of death in sub-Saharan Africa. From 1980 to 2022, there was a gradual decrease in child infections, indicating a good signal of awareness of HIV (WHO and UNAIDS sources) (UNAIDS report, 2023).

Reverse transcriptase (RT), which is crucial for HIV-1 replication, is a significant target for AIDS treatment (Jonckheere et al., 2000). Nucleoside reverse transcriptase inhibitors (NRTIs) compete with natural substrates and act as chain terminators (Clercq, 2000). Non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind differently, as revealed through X-ray crystallography, adopting a 'butterfly-like' conformation (Hajos et al., 2000, Ren et al., 2000, Pedersen and Pedersen, 1999)

Nevirapine, delavirdine, and efavirenz are non-nucleoside reverse transcriptase inhibitors (NNRTIs) currently used as therapeutic agents. These inhibitors, representing diverse groups, specifically target various viral enzymes such as nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors, integrase inhibitors, combination inhibitors, and CCR5 inhibitors (Clercq, 1998). Some of the established NNRTI structures are as follows:

Benzotriazole derivatives, a class of heterocyclic organic compounds characterized by their unique triazole ring structure, have captivated researchers across diverse scientific disciplines (López-Vallejo et al., 2011, Borowski et al., 2003, El-Kardocy et al., 2020, Prichard et al., 1980, Waller, 1994) . These versatile compounds, extensively scrutinized for applications spanning corrosion inhibition to pharmaceutical development, have recently garnered attention as potent anti-HIV agents. The significance of these compounds in the anti-HIV domain stems from their distinctive mode of action coupled with favorable pharmacokinetic and pharmacodynamic profiles. Benzotriazole derivatives are promising candidates for multitargeted treatments, offering reduced side effects and improved patient adherence. Moreover, their synergistic effects in combination with existing antiretroviral therapies demonstrate heightened antiviral activity, presenting potential breakthroughs in managing drug-resistant strains (Kaplan, 2002, Fobofou et al., 2015, Mayer et al., 2009) .

Our investigation, guided by existing scholarly works, focused on synthesizing compounds 3a-j and 6a-j. Afterward, we conducted an exhaustive spectroscopic analysis employing 1H NMR, 13C NMR, and mass spectrometric techniques. Additionally, we explored the in vitro anti-HIV-1 RT activity of benzotriazole derivatives and evaluated the in vivo oral toxicity of the most potent compounds identified during anti-HIV-1 RT studies to confirm the nontoxicity of the potent compounds. After these assessments, molecular docking studies were performed for all synthesized compounds to elucidate potential interactions between the synthesized compounds (ligands) and a target biomolecule (protein) at the molecular level, followed by molecular dynamics studies of potent compounds. We employed the density functional theory (DFT) method to characterize the most potent compound, 1-(4-nitrophenyl)-2-(perbromo-1H-benzo[d] [1–3]triazol-1-yl)ethan-1-one. (3 h). The reactivity regions of compound 3 h were assessed by analyzing its DFT molecular orbitals and electrostatic potential maps. The main objective of this investigation was to address the urgent need for innovative solutions in the field of anti-HIV-1 RT drugs, along with ensuring the safety and effectiveness of potential drugs. The object will be a contribution to public health.