In vitro bioactivities and in silico enzyme interactions of abietatrien-3β-ol by bio-guided isolation from Nepeta italica subsp. italica

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Abietatrien-3β-ol (ATO) was isolated from the aerial part of the Nepeta italica subsp. italica methanol-chloroform extract and studied antioxidant, enzyme inhibition, and DNA protection activities. The plant extract was fractionated by silica gel column chromatography using four different solvents. After the active chloroform fraction was divided into six subfractions under the guidance of bioactivity, ATO was isolated from the fourth active subfraction. The molecular structure of ATO was determined by the NMR techniques and confirmed with literature data. In the antioxidant test, ATO showed excellent DPPH˙ (IC50-1.18 ± 0.11 µg/mL), ABTS˙+ (IC50-1.82 ± 0.00 µg/mL), metal chelating (IC50-2.90 ± 0.05 µg/mL), superoxide anion scavenging (IC50-11.59 ± 0.27 µg/mL), reducing power (A0.5-21.09 ± 1.42 µg/mL), H2O2 (A0.5-57.81 ± 4.54 µg/mL), and phosphomolybdenum reducing (A0.5-124.23 ± 0.69 µg/mL) activities when compared to standards. The DNA protection potential was also found to be strong in Form I (47.89%) and Form II (4.56%) formations. ATO had high inhibitions in AChE (IC50-1.25 ± 0.04 µg/mL), BChE (IC50-1.26 ± 0.03 µg/mL), lipase (IC50-7.58 ± 0.27 µg/mL), and tyrosinase (IC50-9.60 ± 0.03 µg/mL). In molecular docking studies, ATO had a high binding affinity with α-amylase (−8.80 kcal/mol), tyrosinase (−8.10 kcal/mol), and urease (−8.10 kcal/mol) enzymes. In addition, by detailing the interaction of ATO with key enzymes that give the best interactions through molecular docking studies, with molecular dynamics studies, and by performing ADMET and DFT calculations, it was tried to explain that it could be a suitable drug candidate. In light of these studies, ATO is thought to be an effective enzyme inhibitor and a protective molecule against oxidation with its active antioxidant properties.