• Archives of Pharmacal Research
• /
• v.19 no.6
• /
• pp.543-550
• /
• 1996

Analogues of $2(S)-5, 2^{l}, 5^{l}$-trihydroxy-7, 8-dimethoxyflavanone, a naturally-occurring compound, which had been reported to have potent antitumor activity, were synthesized and examined for the cytotoxicity against three cancer cell lines. Among the intermediate chalcones and synthetic 5-hydroxy-7, 8-dimethoxyflavanone analogues, $({\pm})2^{l}, 5^{l}-dibenzyloxy-5, 7, 8-trimethoxyflavanone$ exhibited about 2-8 times stronger activity than $2(S)-5, 2^{l}, 5^{l}$-trihydroxy-7, 8-dimethoxyflavanone against L1210, K562 and A549 cancer cell lines. In the structure-activity relationship, it is suggested that among analogues of 5-hydroxy-7, 8-dimethoxyflavanone, the existence of two oxygenated groups of para-relation at $C-2^{I} and C-5^{I}$ positions on flavanone B-ring, may be necessary to exhibit effective cytotoxic activity.

• Archives of Pharmacal Research
• /
• v.25 no.3
• /
• pp.258-269
• /
• 2002

2-Thiouracil-5-sulfonylchloride 1 reacted with a series of aromatic and heterocyclic amines to give 2a-j. The same compound 1 was reacted with a series of sulphonamides giving different sulphonamides of type 3a-e. On the other hand compound 1 was allowed to react with p-aminoacetophenone givining compound 4 which in turn was allowed to react with derivatives of alkyl thiosemicarbazides to give thiosemicarbazones of type 5a-e, also compound 4 was monobrominated to give compound 6 which in turn was reacted thiosemicarbazones of some aldehydes to give the corresponding thiazole derivatives 7a-f. In the same time compound 4 was reacted with a series of aromatic and heterocyclic aldehydes givining chalcones 8a-g (Claisen-Schemidt reaction). Also compound 4 was allowed to react with a series of aromatic and heterocyclic aldehydes, ethyl cyano acetate and/or malononitrile, and ammonium acetate giving pyridine derivatives 9a-d and 10a-e respectively. The biological effects of some of the new synthesized compounds was also investigated.

• Archives of Pharmacal Research
• /
• v.27 no.5
• /
• pp.507-511
• /
• 2004

From the flowers of Chromolaena odorata (Eupatorium odoratum) four flavanones, isosakuranetin (5,7-dihydroxy-4'-methoxyflavanone) (1), persicogenin (5,3'-dihydroxy-7,4'-dimethoxyflavanone) (2), 5,6,7,4'-tetramethoxyflavanone (3) and 4'-hydroxy-5,6,7-trimethoxyfla-vanone (4), two chalcones, 2'-hydroxy-4,4',5',6'-tetramethoxychalcone (5) and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (6), and two flavones, acacetin (5,7-dihydroxy-4'-methoxyflavone) (7) and luteolin (5,7,3',4'-tetrahydroxyflavone) (8) were isolated and identified. Compound 1 exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis with the MIC value of 174.8 $\mu$M, whereas compounds 4,7, and 8 exhibited weak activity with the MIC values of 606.0, 704.2 and 699.3 $\mu$M respectively. Compound 7 showed moderate cytotoxicity against human small cell lung cancer (NCI-H187) cells with the MIC value of 24.6 $\mu$M, whereas compound 8 exhibited moderate toxicity against NCI-H187 cells and week toxicity against human breast cancer (BC) cells with the MIC values of 19.2 and 38.4 $\mu$M respectively.

• Journal of the Korean Chemical Society
• /
• v.57 no.2
• /
• pp.234-240
• /
• 2013

The synthesis of title compounds were accomplished by synthetic sequence shown in Scheme 1. Chalcones on cyclocondensation with thiourea in ethanol and potassium hydroxide under reflux yielded the respective dihydropyramidin-2(1H)-thiones. Each of the dihydropyrimidin thiones was, then subjected to the Mannich condensation in alkaline medium using three different secondary amines, viz., dimethylamine, diethylamine and morpholine to obtain a new series of S-Mannich bases. All the synthesised compounds ($C_1-C_{15}$) were evaluated for their antiulcer and antibacterial activities. Compounds $C_4$, $C_5$, $C_6$, $C_{14}$ and $C_{15}$ exhibited relatively more potent antiulcer activity but not comparable to the standard; Omeprazole, while $C_1$, $C_2$, $C_3$ and $C_{13}$ were moderate in activity at 100 mg/kg p.o. All the compounds ($C_1-C_{15}$) showed mild to moderate activity against both Gram-positive (S.aureus, L.delbrueckii) and Gram-negative (P.vulgaris, E.coli) bacteria. Amongst the compounds tested, only $C_6$, $C_9$, $C_{12}$ and $C_{15}$ were found to be potent.

• YAKHAK HOEJI
• /
• v.54 no.1
• /
• pp.27-31
• /
• 2010

Xanthohumol, a prenylated chalcone of the Hop plant (Humulus lupulus L.), has been reported to suppress tumor growth. 4-hydroxychalcone and isobavachalcone are chalcone derivatives and they have similar structure with xanthohumol. In the present study, we investigated the cytotoxic activities of chalcone and its derivatives, 4-hydroxychalcone, xanthohumol, and isobavachalcone, in MCF-7 and adriamycin resistant MCF-7 (MCF-7/ADR) breast cancer cells and HT-1080 fibrosarcoma cells. In a cell viability assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reagent, chalcone and 4-hydroxychalcone decreased cell viability in HT-1080 cells, but not in MCF-7 and MCF-7/ADR cells. Isobavachalcone showed similar cytotoxicity in HT-1080 cells, and only limited cytotoxicity in MCF-7 and MCF-7/ADR cells at very high concentration (50 ${\mu}M$). In contrast, xanthohumol showed concentration-dependent cytotoxicity in MCF-7, MCF-7/ADR, and HT-1080 cancer cells. Taken together, the structure-activity relationship of chalcone and its derivatives indicate that chalcones may be valuable cytotoxic compounds against selective cancer types.

• Journal of the Korean Chemical Society
• /
• v.65 no.2
• /
• pp.113-120
• /
• 2021

New phenylthiophenechalcones,1-(biphenyl-4-yl)-3-(5-phenylthiophen-2-yl)prop-2-en-1-one (3a) and 3-(5-phenylthiophen-2-yl)-1-(4-(piperidin-1-yl) phenyl) prop-2-en-1-one (3b) were synthesized, next, their treatment with thiosemicarbazide in ethanol afforded their pyrazoline derivatives (4a) and (4b), respectively. The molecular structures of the synthesized compounds were confirmed via elemental analysis, FT-IR, 1H, 13C NMR and mass spectroscopy. The geometrical elucidation of four suggested conformers has been studied for these compounds. DFT calculations have been performed to study the stability and the structural parameters of the predicted conformers and revealed that orientation of the biphenyl and the phenylthiophene moieties affect the stability of the estimated conformers of the synthesized chalcones and pyrazoline. Moreover, two reaction mechanisms have been proposed to illustrate the reaction products and the DFT calculations have been used to confirm the reaction mechanism of the pyrazoline compounds.

• Biomolecules & Therapeutics
• /
• v.23 no.2
• /
• pp.119-127
• /
• 2015

Chalcones (1,3-diaryl-2-propen-1-ones), a subfamily of flavonoid, are widely known to possess potent anti-inflammatory and anti-oxidant properties. In this study, we investigated the effect of 3-(4-Hydroxyphenyl)-1-(thio3-(4-Hydroxyphenyl phen-2-yl)prop-2-en-1-one (TI-I-175), a synthetic chalcone derivative, on endotoxin-induced expression of monocyte chemoattractant protein-1 (MCP-1), one of the key chemokines that regulates migration and infiltration of immune cells, and its potential mechanisms. TI-I-175 potently inhibited MCP-1 mRNA expression stimulated by lipopolysaccharide (LPS) in RAW 264.7 macrophages without significant effect on cell viability. Treatment of cells with TI-I-175 markedly prevented LPS-induced transcriptional activation of activator protein-1 (AP-1) as measured by luciferase reporter assay, while nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity was not inhibited by TI-I-175, implying that TI-I-175 suppressed MCP-1 expression probably via regulation of AP-1. In addition, TI-I-175 treatment significantly inhibited LPS-induced Akt phosphorylation and led to a significant decrease in reactive oxygen species (ROS) production by LPS, which act as up-stream signaling events required for AP-1 activation in RAW 264.7 macrophages. Taken together, these results indicate that TI-I-175 suppresses MCP-1 gene expression in LPS-stimulated RAW 264.7 macrophages via suppression of ROS production and Akt activation.

• The Korea Journal of Herbology
• /
• v.32 no.6
• /
• pp.1-7
• /
• 2017

Objectives : The heartwood of Sappan Lignum has been used since ancient times as an ingredient in folk medicines against anti-bacterial and anti-anemia purposes. Many bioactive constituents have been derived from this biomass such as chalcones and homoisoflavonoids. In the current investigation, the antioxidant and anti-diabetic properties using DPPH and $ABTS^+$ radicals scavenging, ${\alpha}-glucosidase$, and advanced glycation end products (AGEs) inhibition assays were evaluated by different extraction methods of Sappan Lignum. Methods : In our continuing investigation for bioactive natural ingredients, the antioxidant and ${\alpha}-glucosidase$ inhibitory properties of Sappan Lignum extracts were prepared from different extraction methods and the biological efficacies were investigated in vitro. The antioxidant properties were evaluated employing radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) ($ABTS^+$) radicals. In addition, the anti-diabetic effects of Sappan Lignum extracts were tested via ${\alpha}-glucosidase$ and AGEs formation inhibitory assay. The total phenolic contents were determined using a spectrophotometric method. Results : All the tested samples showed dose-dependent radical scavenging and ${\alpha}-glucosidase$ inhibitory activities. Among the tested extracts, the 80% methanolic extract of Sappan Lignum was showed the most potent activity with an $IC_{50}$ value of $82.3{\pm}1.7{\mu}g/m{\ell}$ against DPPH radical scavenging assay. While, $ABTS^+$ radical scavenging activity of 80% methanolic extract was higher than those of other extracts. Also, ${\alpha}-glucosidase$ inhibitory and AGEs formation effects of each extacts and total phenolic contents were evaluated. Conclusions : These results suggested that Sappan Lignum can be considered as a new effective source of natural antioxidant and anti-diabetic materials.

• Applied Biological Chemistry
• /
• v.43 no.2
• /
• pp.95-99
• /
• 2000

A series of hetero ring (X) substitued chalcone derivatives with farnesyl protein transferase (FPTase) inhibition activities $(pI_{50})$ values determined in vitro is analyzed by modified Free-Wilson (F-W) and Hansch method for quantitative structure activity relationship (QSARs). On the basis of F-W analysis on the FPTase inhibitory activity of a training set of the compounds, none of the (X)-substituents were not contribute the activity. But the net charge of ${\alpha}$ carbon atom is contribute the activity than that of ${\beta}$ carbon atom. And the relative orders of the (Y)-substituents on the activity are ortho>meta>para-substituents. According to Hansch approach, the activities would depend largely on the optimal, $(R_{opt.}=-0.35)$ resonance effect with ortho substituted $(I_o>0)$ electron donating group (R<0) and STERIMOL parameter, $B_1$ constant. The inhibition activity between hetro ring substituents have been a proportioned with each others and none substituent(H), 45 showed the highest FPTase inhibition $(pI_{50}=4.30)$ activity.