Exploring Ocimum basilicum-derived indole alkaloid: A dual approach of antibacterial effects and computational study into enzymatic inhibition of Streptococcus sanguinis

Streptococcus sanguinis is the first bacteria to form biofilms on teeth surface. Biofilms are formed by several enzymatic mechanisms, such as PilC, Sortase C, Gtf, and LuxS. The aim of this study was to isolate indole compound from Ocimum basilicum leaves, to evaluate the activity against S. sanguinis by experimental studies and the inhibitory mechanism against enzymatic systems in biofilm by computational studies. Isolation was performed using column chromatography and characterized by LC/MS/MS, 1 H NMR, 13 C NMR, HMQC, HMBC, and COSY. The activity test was determined by inhibition zone, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). Biofilm mechanism was predicted by molecular docking. The results showed that 1 H -indole-3-carbaldehyde ( 1 ) of 65.8 mg was successfully isolated from O. basilicum leaves. Compound 1 gave an inhibition zone of 11.85 mm and MIC of 625 μg.mL −1 . The molecular docking showed that the indole groups (compounds 1 – 11 ) had more potential to inhibit Gtf than PilC, SrtC, and LuxS. Binding affinity of compound 11 gave the strongest activity in inhibiting Gtf. Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) analysis showed that compound 11 tended to be toxic and very unfavourable in metabolic system, so it was more potential to be non-oral drug candidate. While compound 7 was the only compound that was within the allowable range in five ADMET parameters. Therefore, compound 7 was more potential as oral drug candidate because it also had a stronger binding affinity to Gtf than the other three enzymes. The chemical interaction showed that less electronegative compounds better inhibited Gtf. • 1H-indole-3-carbaldehyde from Ocimum basilicum active to Streptococcus sanguinis . • (E)-3-(7-hydroxyindol-3-yl)acrylic acid is potentially as oral drug to inhibit Gtf. • Chondriamide A is potentially as non-oral drug with the highest inhibition to Gtf. • Less electronegative indoles are better at inhibiting SrtC and Gtf. • More electronegative indoles are better at inhibiting PilC and LuxS.