Jutatip Boonsombat

A divergent synthetic approach to marine meroterpenoids from the naturally abundant chiral pool precursor anticopalic acid is described. A gram-scale intermediate was prepared in four steps (74.5% yield), enabling access to a synthetic sequence that delivered structurally diverse meroterpenoids. This strategy enabled the first syntheses of fascioquinol A, fascioquinol B, and strongylophorine-22, along with concise syntheses of makassaric acid and the dehydro analogs of fascioquinols C and D. These results demonstrate the utility of abundant natural products as chiral pool feedstocks for divergent synthesis of marine meroterpenoid frameworks.

The concise total synthesis of habiterpenol utilizing the highly abundant natural product, anticopalic acid, as a chiral pool starting material is presented in this work. The key synthetic transformations involved the acid‐induced cyclization of the bicyclic anticopalic acid to directly construct the C‐ring of the habiterpenol framework and the aromatic Nazarov cyclization to afford the pentacyclic ring‐fused indane core structure. The synthesis was completed in 10 steps with an overall yield of 17.3%. All carbon atoms present in anticopalic acid were incorporated into the habiterpenol structure, highlighting the atom economy of this synthesis. Density functional theory (DFT) calculations were performed to gain insight into and explain specific reaction outcomes. Additionally, various assays were conducted to evaluate the chemopreventive properties of habiterpenol and related pentacyclic derivatives, providing new biological insights into these compounds. This study demonstrates the effectiveness of the chiral pool approach, using a high‐abundance natural product as a starting material to access a low‐abundance natural product valuable for biological activity exploration. The potential application of this strategy to the total synthesis of similar terpenoid scaffolds offers valuable opportunities for medicinal chemistry and drug development.

Lysiphyllum binatum (Blanco) de Wit in the Fabaceae family, despite its traditional medicinal uses, has not been the subject of prior scientific inquiry in

Anticopalic acid (ACP), a labdane type diterpenoid obtained from Kaempferia elegans rhizomes, together with 21 semi-synthetic derivatives, were evaluated for their cancer cytotoxic activity. Most derivatives displayed higher cytotoxic activity than the parent compound ACP in a panel of nine cancer cell lines. Among the tested compounds, the amide 4p showed the highest cytotoxic activity toward leukemia cell lines, HL-60 and MOLT-3, with IC₅₀ values of 6.81 ± 1.99 and 3.72 ± 0.26 µM, respectively. More interestingly, the amide derivative 4l exhibited cytotoxic activity with an IC₅₀ of 13.73 ± 0.04 µM against the MDA-MB-231 triple-negative breast cancer cell line, which is the most aggressive type of breast cancer. Mechanistic studies revealed that 4l induced cell death in MDA-MB-231 cells through non-apoptotic regulated cell death. In addition, western blot analysis showed that compound 4l decreased the phosphorylation of FAK protein in a concentration-dependent manner. Molecular docking simulations elucidated that compound 4l could potentially inhibit FAK activation by binding to a pocket of FAK kinase domain. The data suggested that compound 4l could be a potential FAK inhibitor for treating triple-negative breast cancer and worth being further investigated.

Psoralen derivatives are well known for their unique phototoxicity and also exhibits promising anti-breast cancer activity both in the presence and the absence of UVA irradiation. However, the structure–activity relationship on this scaffold remains lacking. Herein, a series of psoralen derivatives with various C-5 substituents were synthesized and evaluated for their in vitro dark and light-activated cytotoxicity against three breast cancer cell lines: MDA-MB-231, T47-D, and SK-BR-3. The type of substituents dramatically impacted the activity, with the 4-bromobenzyl amide derivative (3c) exhibiting the highest dark cytotoxicity against T47-D (IC₅₀ = 10.14 µM), with the activity comparable to those of the reference drugs (doxorubicin, 1.46 µM; tamoxifen citrate, 20.86 µM; lapatinib 9.78 µM). On the other hand, the furanylamide 3g exhibits the highest phototoxicity against SK-BR-3 cells with the IC₅₀ of 2.71 µM, which is almost tenfold increase compared to the parent compound, methoxsalen. Moreover, these derivatives showed exceptional selectivity towards HER2+ (SK-BR-3) over the HER2− (MDA-MB-231) breast cancer cell lines, which correlates well with the results from the molecular docking study, revealing that 3g formed favorable interactions within the active site of the HER2. Additionally, the cell morphology of SK-BR-3 cells suggested that the significant phototoxicity was related to induction of cell apoptosis. Most of the synthesized psoralen derivatives possess acceptable physicochemical properties and are suitable for being further developed as a novel anti-breast cancer agent in the future.

Target cancer drug therapy is an alternative treatment for advanced hepatocellular carcinoma (HCC) patients. However, the treatment using approved targeted drugs has encountered a number of limitations, including the poor pharmacological properties of drugs, therapy efficiency, adverse effects, and drug resistance. As a consequence, the discovery and development of anti-HCC drug structures are therefore still in high demand. Herein, we designed and synthesized a new series of 1,2,3-triazole-cored structures incorporating aryl urea as anti-HepG2 agents. Forty-nine analogs were prepared via nucleophilic addition and copper-catalyzed azide-alkyne cycloaddition (CuAAC) with excellent yields. Significantly, almost all triazole-cored analogs exhibited less cytotoxicity toward normal cells, human embryonal lung fibroblast cell MRC-5, compared to Sorafenib and Doxorubicin. Among them, 2m’ and 2e exhibited the highest selectivity indexes (SI = 14.7 and 12.2), which were ca. 4.4- and 3.7-fold superior to that of Sorafenib (SI = 3.30) and ca. 3.8- and 3.2-fold superior to that of Doxorubicin (SI = 3.83), respectively. Additionally, excellent inhibitory activity against hepatocellular carcinoma HepG2, comparable to Sorafenib, was still maintained. A cell-cycle analysis and apoptosis induction study suggested that 2m’ and 2e likely share a similar mechanism of action to Sorafenib. Furthermore, compounds 2m’ and 2e exhibit appropriate drug-likeness, analyzed by SwissADME. With their excellent anti-HepG2 activity, improved selectivity indexes, and appropriate druggability, the triazole-cored analogs 2m’ and 2e are suggested to be promising candidates for development as targeted cancer agents and drugs used in combination therapy for the treatment of HCC.