Cathepsin B, an abundant expressed cysteine peptidase, plays a key role in cancer cell proliferation, tumor metastasis, apoptosis, angiogenesis, invasion and migration. Therefore, development of cathepsin B inhibitors to treat cancer is of great significance. In this study, dihydronaphthalenone chalconoid derivatives containing different benzyliden moieties were synthesized via an efficient route in microwave condition that resulted in the desired compounds in high yields compared to acid- or base-catalyzed refluxing conditions. Cytotoxicity of the compounds was evaluated against K562, HT-29 and MCF-7 human cancer cell lines by MTT assay. P1, P3 and P9 (containing 4-OCH3, 3-NO2 and 4-CN moieties on phenyl ring, respectively) exhibited good cytotoxic activity with an IC50 range of 7.1-28.9 μM. Molecular docking analysis was carried out to investigate the possible interactions and binding modes of all compounds with cathepsin B. The most promising compounds, P1, P3 and P9 were well accommodated within the active site and had the least estimated free binding energies. It was concluded from both MTT assay and docking studies that some dihydronaphthalenone chalconoid derivatives could be suggested as effective cytotoxic agents and potential cathepsin B inhibitors

ABSTRACT Salvia lachnocalyx Hedge, Lamiaceae, is an endemic sage which grows naturally in the Fars Province of Iran. The phytochemical analyses of the roots of S. lachnocalyx led to the isolation of five known diterpenoids: ferruginol (1), taxodione (2), sahandinone (3), 4-dehydrosalvilimbinol (4) and labda-7,14-dien-13-ol (5). Their chemical structures were elucidated using one (1H and 13C) and two dimensional (COSY, HSQC and HMBC) NMR spectroscopic data as well as electron impact mass spectra. The cytotoxicity of the purified compounds was evaluated against three human cancer cell lines; MOLT-4 (acute lymphoblastic leukemia), HT-29 (colorectal adenocarcinoma) and MCF7 (breast adenocarcinoma) and all of the isolated compounds showed considerable cytotoxic activity against these cell lines. Compounds 2 and 3 (IC50 range: 0.41–3.87 µg/ml) with endocyclic α,β-unsaturated carbonyl functional group, exhibited the highest cytotoxic activities compared to the other compounds (IC50 range: 6.85–17.23 µg/ml). In conclusion, compounds 2 and 3 are presented as compounds that deserve further investigation of their biological activities.

ABSTRACT Different solvent extracts of Dichotomaria obtusata (J. Ellis & Solander) Lamark, Galaxauraceae, a red algae collected from the coast of Bushehr in the Persain Gulf, was investigated for its cytotoxic properties and chemical constituents. The fresh alga, after extraction with methanol and dichloromethane were combined and partitioned between water, dichloromethane and ethyl acetate. The above fractions were then tested against MOLT-4 (human lymphoblastic leukemia) cancer cell line. The IC50 values of the dichloromethane and ethyl acetate layers of the crude extract were 29.8 ± 3.1 and 30.6 ± 7.9 µg/ml against MOLT-4 cells, respectively, while the water layer showed a week activity with IC50 > 50 µg/ml. After fractionation of the active extracts using open column chromatography over silica gel and preparative thin layer chromatography purification, two terpenoid derived compounds, trans-phytol palmitate and γ-tocopherol were isolated from the dichloromethane and ethyl acetate extracts. The structures of the compounds were elucidated using different spectral data including 1H NMR, 13C NMR, HSQC, HMBC and EI-MS. The IC50 values of compounds trans-phytol palmitate, γ-tocopherol and an undetermined mixture of compounds (F-13-14) were determined as 43.4 ± 1.6, – and 20.3 ± 6.2 µg/ml against LS180 (human colon adenocarcinoma); 53.2 ± 9.3, >100 and 27.6 ± 6.9 µg/ml against MCF-7 (human breast adenocarcinoma) and 40.0 ± 4.1, 48.8 ± 1.8 and 15.9 ± 0.3 µg/ml against MOLT-4 cell lines, respectively, which were comparable to the IC50 values of standard anticancer agent, cisplatin against the same cell lines. The red algae collected from the Persian Gulf contained substances that could inhibit the growth of human cancer cell lines and may represent a natural source for the discovery of novel anticancer agents.