Department of Chemical Engineering, College of Engineering, University of the Philippines Diliman, Quezon City, Philippines
Email: obagua@up.edu.ph (O.F.B.A.); ritamargo@up.edu.ph (R.J.I.T.)
*Corresponding author
Manuscript received February 28, 2025; accepted May 11, 2025; published June 13, 2025
Abstract—Viral and bacterial infections are still prevalent worldwide. Infection with the Human Immunodeficiency Virus (HIV) causes Acquired Immunodeficiency Syndrome (AIDS), and in 2023, around 39.9 million people across the globe were living with HIV/AIDS. On the other hand, bacterial infections account for 15% of global deaths, despite the discovery of antibiotics, due to bacterial drug resistance. Developing new, selective, and safe inhibitors for the treatment of these diseases remains a high priority for medical research. Many indole derivatives have specifically been used in pharmaceutical applications. By targeting HIV-1 glycoprotein 120 (gp 120) and FabH (β-ketoacyl-acyl carrier protein (ACP) synthase III) enzymes, 3-sulfenylated indoles have shown promise in HIV-1 gp 120 and FabH inhibition, respectively. In this study, previously synthesized indole derivatives, using a newly developed protocol involving sulfa-Michael addition and intramolecular reductive N-heteroannulation, are assessed for their antiviral and antibacterial activity. Toxicity analysis and molecular docking is performed on twenty-seven indole derivatives to assess their affinity against the targets. Among the 27 compounds, compound 5b, phenyl(3-(p-tolylthio)-1H-indol-2-yl)methanone, with a binding score of -8.91 kJ, was found to be the most potent HIV-1 gp 120 inhibitor, while compound 5a, phenyl(3-(phenylthio)-1H-indol-2-yl)methanone, with a binding score of -7.96 kJ, showed the most promise against FabH inhibition. Interaction diagrams indicate that the affinity of the studied indole-based derivatives is governed by hydrogen bonding (H-bond), which occurs either with a nitrogen or oxygen atom of the indole group, as well as hydrophobic and pi interactions within the binding pocket. Upon comparison with compounds previously assessed for their HIV-1 gp 120 and FabH inhibition abilities, respectively (r1-r4), it is found that the new compounds compare favorably with the reference compounds in terms of binding score. Analysis of results show that the indole-based analogs can be a starting point for the synthesis of drugs designed as both antiviral and antibacterial agents.
Keywords—FabH, HIV-1, indole derivative, molecular docking, toxicity analysis
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Cite: Olivia Francesca B. Agua and Ramuel John I. Tamargo, "Molecular Docking Studies of 3-thioindoles as Potent Antiviral and Antibacterial Agents," International Journal of Chemical Engineering and Applications vol. 16, no. 1, pp. 68-76, 2025.
