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A simple and economical method was developed for the extraction and isolation of pentacyclic triterpenoid lantadene A from the leaves of Lantana camara. The lantadene A displays significant anti-in...

Natural products and their scaffolds encompasses an array of molecular entities as starting points for drug designing and discovery. In the past two decades, phytochemically driven Lantadenes and their modified analogues have attracted lots of attention due to their tumor necrosis factor-α induced nuclear factor-kappa B inhibition and consequently their promising anticancer potential. Earlier reports described the synthesis of esters at C-3 and C-22 of pentacyclic triterpenoid Lantadene, and their evaluation to inhibit tumor necrosis factor-α induced nuclear factor-kappa B along with cytotoxicity against A549 lung cancer cells. In the modern drug discovery process, molecular docking have become an integral part of drug design. Combination of computational platforms and experimental strategies have allowed many successful stories in the discovery of new structure-based or mechanism drugs. Thus as a continuation of our research concerning Lantadenes and their significance, present study has been undertaken to predict binding mode, pharmacokinetic and drug likeness using Vlife MDS Biopredicta and ADMETlab tools. In silico inspired grip docking approach was utilized to estimate binding interactions of all the optimized Lantadenes and their modified ester against nuclear factor-kappa B receptor (PDB ID: 1LE9). In addition, all the compounds were screened for pharmacokinetic profile and drug likeness as an important consideration for the selection of compounds with desirable prosperities using ADMETlab tools. Ligand-receptor analysis revealed Lantadene parent nuclei and their modified analogues as potent inhibitors of nuclear factor-kappa B receptor based on binding energy (-21.16 to -42.56 kcal/mol), number of interactions and bond length. Furthermore, most of the analogues were found to have good ADMET profiles. Cumulative computational analyses provided the lead Lantadene analogue 10 and can be considered as a potential candidate for detailed mechanistic studies against lung cancer.

A simple and economical method was developed for the extraction and isolation of pentacyclic triterpenoid lantadene A from the leaves of

The increased cases of hyperpigmentation and other related dermatological problems in human beings have led to the development of a number of tyrosinase inhibitors. In the present study, we have used a docking algorithm to simulate binding between tyrosinase and hydroxy-substituted (Z)-3-benzylideneindolin-2-one chalcones and studied the inhibition of tyrosinase. The results of virtual screening studies indicated that the estimated free energy of binding of all the docked ligands ranged between −8.08 and −4.27 kcal/mol, while their estimated inhibition constants (Ki) were found to be between 1.20 and 736.75 µM. Among all the compounds docked, 2,4,6-trihydroxy-substituted chalcone (11) showed the lowest estimated free energy of binding followed by dihydroxy and monohydroxy-substituted analogs. In the in vitro tyrosinase inhibition assay, 11 displayed an IC50 of 46.26 µM. Moreover, in ADMET study, 11 was found to be safe and non-toxic. The present study suggested that the strategy of predicting tyrosinase inhibition based on hydroxy-substituted (Z)-3-benzylideneindolin-2-one chalcones and their orientation would be useful for developing novel potent tyrosinase inhibitors.

The ATR pathway is a critical mediator of the replication stress response in cells. In aberrantly proliferating cancer cells, this pathway can help maintain sufficient genomic integrity for cancer cell progression. Herein we describe the discovery of 19, a pyrazolopyrimidine-containing inhibitor of ATR via a strategic repurposing of compounds targeting PI3K.

The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.