Abstract::
Three compounds from Andrographis paniculata (Burm. f) Nees leaf were isolated and identified
using 1H, 13C, 2D-NMR, and HR-MS techniques for the first time. Compound 3,19-Di-Oacetylandrographolide
(3,19-DAA) or (4) is produced by acetylating compound (2). Compounds (2) and (4)
have been investigated for their cytotoxic effects on three human cancer cell lines (SK-LU-1, Hela, and
HepG2) using the MTT method. Compound (4) demonstrated significant cytotoxicity against all three cancer
cell lines, with IC50 values ranging from 8.38 to 10.15 μM. This represents an increase in cytotoxicity of 2.67
to 3.12-fold compared to compound (2). One way to deal with the problem of low water solubility is by encapsulating
(4) into liposomes using a thin-film hydration technique. The optimal conditions for maximizing encapsulation
efficiency involve molar ratios of phosphatidylcholine, 3,19-DAA, and cholesterol at 4:1:1. Encapsulating
compound (4) within nanoscale liposomes increases its water solubility compared to the free form of
compound (4). Pose 324 of compound (4) demonstrated the best conformation among 500 docking conformations
when docked to enzyme 1T8I in a silico docking study. The free Gibbs energy and inhibition constant
were determined to be -7.09 Kcal/mol and 6.32 μM, respectively. These values help elucidate the strong interaction
between compound (4) and the enzyme in the ligand interaction model. The molecular dynamics simulation
using Desmond software in the Linux environment was conducted for a duration of 0 to 100 nanoseconds
on the complex formed by pose 324 and 1T8I. The results showed effective interactions within the complex,
with stability observed from 0 to 60 nanoseconds. Throughout the simulation, specific amino acids such as Ala
499 (involved in 90% of the simulation time with hydrogen bonding via a water bridge) and Thr 501 (involved
in 50% of the simulation time with one hydrogen bond via a water bridge) were found to play significant roles.
The majority of torsion bondings are C-O bondings in the acetyl group of compound (4), with torsion energy
values of 13.47 Kcal/mol. Carbon atom C-29 at position 324 exhibits the highest fluctuation.
