Isolation, Cytotoxicity Evaluation, Docking, ADMET and Drug Likeness Studies of Secondary Metabolites from the Stem Bark of Anthocephalus cadamba (Roxb.)

Abstract

Phytochemical investigation of the stem bark of Anthocephalus cadamba(Rubiaceae) led to the isolation of total ten secondary metabolites (1‐10) including β–sitosterol (1), ursolic acid (2), vanillic acid (3), quinovic acid (4), 3‐O‐[α‐L‐rhamnopyranosyl]‐quinovic acid (5), β‐sitosterol β‐D‐glucoside (6), cadambine (7), 3β‐dihydrocadambine (8), 7‐O‐acetyl loganin (9) and hexyl p‐coumarate (10). Four acetylated derivatives 2 a,5 a,7 aand8 aobtained through acetylation of compounds 2, 5, 7 and 8 respectively. All the compounds characterized using 1H and 13CNMR, HRESIMS and IR and comparison with literature. Compound 4showed the best cytotoxic activity with IC50 value 4 and 7 μM against pancreatic (MIA‐pa‐Ca‐2) and leukemia (HL‐60) cancer cells respectively. Docking results supported the anticancer potential of compound 4via inhibition of EGFR receptor (PDB ID:3POZ) and its pharmacokinetic profile found optimized as per the Lipinski's filter. Therefore compound 4has the potential to be developed as an anticancer agent against pancreatic cancer cells.

Management of inflammatory disorders: A brief review of selected ethnomedicinal plants

“…8) etc. have been reported from this plant, where quinovic acid demonstrated potential anticancer property [115]. In another study, several other compounds have been reported from this plant including vincosamide-N-oxide and isodihydroamino cadambine, vincosamide, vallesiachotamine, iso-vallesiachotamine, and oleanolic acid etc., among which vallesiachotamine, iso-vallesiachotamine have shown potent anticancer activity against cancer cell line whilst all of the identified compounds did not show any toxic effect on normal cells [116].…”

Computational Bioprospecting Guggulsterone against ADP Ribose Phosphatase of SARS-CoV-2

“…A semi-empirical force field was utilized to predict the ligand’s binding energy concerning the specific macromolecular target. The force field predicts the binding energy of the ligand by allowing the integration of intra-molecular energies through evaluation of the energies for their bound and unbound states based on a comprehensive thermodynamic model [ 44 , 45 , 46 ]. The parameters required for docking of the ligand molecule were saved in a file named the docking parameter file [ 38 ].…”

“…Traditional plants considered in the current study included Allium sativum , Camellia sinusis , Zinger officinale , Nigella sativa , Punica granatum , Curcuma longa , Glycyrrhiza glabra , Taraxacum , Thymus vulgaris , Ocimum tenuiflorum , Phyllanthus emblica Linn., Trigonella foenum , Piper nigrum , etc. The above-mentioned plants have been reported for the presence of alkaloids, terpenoids, saponins, steroids, glycosides, carbohydrates, monosaccharides, and soluble starch [ 45 , 46 ]. Thus, the prepared ligand library was employed to perform virtual screening with the ARP enzyme, with the intent to identify possible leads.…”

“…The molecular dynamic simulation was magnified to 100 ns for the ligand guggulsterone, based on the stability within the macromolecular complex observed in the MD simulation for a shorter period of 10 ns. The TIP3P explicit water model was used to create an orthorhombic-shaped simulation box with a 10 Å gap between the wall of the box and the ligand-protein complex [ 11 , 20 , 24 , 43 , 45 , 46 , 47 , 48 ]. The simulation box’s isosmotic environment was created by adding counter ions with 0.15 M NaCl to neutralize the existing charge.…”

“…A steady 300 K temperature with 1.013 bars of pressure was maintained throughout the simulation process. To construct simulation interaction graphs after the simulation process, the trajectory path was defined as 9.6 with an energy interval of 1.2 ps [ 11 , 20 , 24 , 43 , 45 , 46 , 47 , 48 ].…”