• YAKHAK HOEJI
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• v.42 no.2
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• pp.159-164
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• 1998

The secondary hydroxy group at side chain of shikonin structure was selectively acylated with various haloacetic acids in presence of dicyclohexylcarbodiimide and 4-dimethylamin opyridine to produce haloacetylshikonin derivatives. The cytotoxicity of monohaloacetylshikonin derivatives against L1210 cells increased in the following order; monochloroacetylshikonin ($ED_{50}$, 0.142${\mu}$g/ml) > monobromoacetylshikonin ($ED_{50}$. 0.158${\mu}$g/ml) > monoiodoacetylshikonin ($ED_{50}$, 0.173${\mu}$g/ml). Introduction of larger halogen atoms decreased the cytotoxic activity, presumably due to steric hinderance. The cytotoxicity of chloroacetylshikonin derivatives was dependent on the number of chlorine atom, thus increasing in the following order; trichloroacetylshikonin (0.032${\mu}$g/ml) > dichloroacetylshikonin (0.059${\mu}$g/ml) > monochloroacetylshikonin ($ED_{50}$, 0.142${\mu}$g/ml). Thus, the electron withdrawing effect seems to be important for the cytotoxicity of chloroacetylshikonin derivatives. Consistent with the above, dichloroacetylshikonin (T/C. 182%) and trifluoroacetylshikonin (195%) showed higher T/C values than monochloroacetyl-(T/C, 122%), monobromoacetyl-(T/C, 154%) and monoiodoacetylshikonin (T/C, 117%) derivatives. Haloacetylshikonin derivatives showing lower cytoxic activities against L1210 cells exhibited lower T/C values. It seems that there is a relationship between the cytoxicity of haloacetylshikonin and their antitumor activity.

• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.79-85
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• 2009

Polyphenolic compounds are reported to have various pharmacological activities such as anti-oxidative, anti-cancerous, anti-inflammatory and anti-aging effects. Although numerous papers explore their functional roles in many different cellular actions, not many studies handle their structural features in anti-inflammatory responses. In this study, therefore, we examined structural role of substituted transstilbenes in their NO inhibitory and NF-${\kappa}B$ suppressive activities. Of 10 compounds tested, 4 compounds (cinnamic acid, resveratrol, piceatannol and curcumin) displayed NO inhibitory activities in a dose-dependent manner. Similarly, these compounds blocked LPS-induced cytotoxicity of RAW264.7 cells. All NO inhibitory compounds also inhibited $I{\kappa}B{\alpha}$ phosphorylation, a hallmark for NF-${\kappa}B$ activation. However, these inhibitory compounds exhibited distinct suppressive pattern in tumor necrosis factor (TNF)-${\alpha}$- or phorbol-12-myristate-13-acetate (PMA)-induced NF-${\kappa}B$ and AP-1 activation. According to structure-activity relationship study, polarity and size of ring B seem to be important for diminishing NO production. Therefore, our data suggest that substituted trans-stilbenes can be developed as novel anti-inflammatory drug or further developed as lead compounds for another improvement.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.215-221
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• 2020

Background: Panax ginseng has been used for a variety of medical purposes in eastern countries for more than two thousand years. From the extensive experiences accumulated in its long medication use history and the substantial strong evidence in modern research studies, we know that ginseng has various pharmacological activities, such as antitumor, antidiabetic, antioxidant, and cardiovascular system-protective effects. The active chemical constituents of ginseng, ginsenosides, are rich in structural diversity and exhibit a wide range of biological activities. Methods: Ginsenoside constituents from P. ginseng flower buds were isolated and purified by various chromatographic methods, and their structures were identified by spectroscopic analysis and comparison with the reported data. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H- tetrazolium bromide method was used to test their cytotoxic effects on three human cancer cell lines. Results: Six ginsenosides, namely 6'-malonyl formyl ginsenoside F₁ (1), 3β-acetoxyl ginsenoside F₁ (2), ginsenoside Rh₂₄ (6), ginsenoside Rh₂₅ (7), 7β-hydroxyl ginsenoside Rd (8) and ginsenoside Rh₂₆ (10) were isolated and elucidated as new compounds, together with four known compounds (3-5 and 9). In addition, the cytotoxicity of these isolated compounds was shown as half inhibitory concentration values, a tentative structure-activity relationship was also discussed based on the results of our bioassay. Conclusion: The study of chemical constituents was useful for the quality control of P. ginseng flower buds. The study on antitumor activities showed that new Compound 1 exhibited moderate cytotoxic activities against HL-60, MGC80-3 and Hep-G2 with half inhibitory concentration values of 16.74, 29.51 and 20.48 μM, respectively.

• Bulletin of the Korean Chemical Society
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• v.35 no.9
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• pp.2809-2812
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• 2014

The 43-residue defensin-like peptide coprisin, which is isolated from dung bettle, Copris tripartitus, is a potent antimicrobial peptide. In our previous work, we determined the tertiary structure of coprisin and found that alpha helical region of coprisin from residue 19 to residue 30 is important for its antimicrobial activities. Here, we designed cop12mer and cop9mer analogs of coprisin based on the tertiary structure of coprisin. To investigate the relationship between hydrophobicity and antimicrobial activities and develop the potent peptide antibiotics, we designed cop9mer-1 with substitution of $His^2$ with Trp in cop9mer. The results showed that cop9mer-1 has higher toxicities as well as improved antimicrobial activities compared to cop9mer. In order to reduce the toxicity of cop9mer-1, we designed cop9mer-2 and cop9mer-3 with substitution of $Cys^3$ with Lys or Ser. Substitution of $Cys^3$ with these hydrophilic amino acids results in lower cytotoxicities compared to cop9mer-1. Cop9mer-2 with substitution of $Cys^3$ with Lys in Cop9mer-1 showed high antibacterial activities against drug resistant bacteria without cytotoxicity. Antibiotic action of cop9mer-1 analog appears to involve permeabilization of the bacterial cell membrane while cop9mer-2 and cop9mer-3 may have different mechanism of action. These results imply that that optimum balance in hydrophobicity and hydrophilicity in these 9-meric peptides plays key roles in their antimicrobial activities as well as cytotoxicities.

• Archives of Pharmacal Research
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• v.24 no.4
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• pp.276-280
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• 2001

Substituted isoquinolin-1-ones (1) were synthesized to test their in vitro anticancer activity. 3-Biphenyl-H-methylisoquinolin-1-one (7) showed the most potent anticancer activity against five different human cancer cell lines.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.230.1-230.1
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• 2002

In this study, anti-cancer effect of N-phenyl-O-phenylthionocarbamate (PPTC) substitutes was investigated. and the apoptotic mechanism by these substrates was examined on SK-MEL -28 human skin cancer cell line. SK-MEL -28 cell was treated at various concentrations for 48hr. and then MTT assay was performed to gain IC$\sub$50/ value and examine cytotoxicity of PPTC substitutes, and quantitative structure-activity relationship (QSAR) between cell and these PPTC substitutes was examined. (omitted)

• Proceedings of the Ginseng society Conference
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• 1988.08a
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• pp.19-24
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• 1988

We have isolated two new cytotoxic polyynes against $L_{1210}$ cell from the root of Panax ginseng. namely acetylpanaxydol and panaxydolchorhydrin. The epoxy group in C-9 and the heptyl group on C-10 of the panaxydol-analogues potentiate the activity. Panaxydol has cis-configuration in epoxy group. There is no diffrernce in activity between cis-. trans- and cis/trans-configurational isomers. The essential structure for the cytotoxicity of panaxydol and its isomers is hept-l-en-4.6-diyn-3-ol.

• Bulletin of the Korean Chemical Society
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• v.32 no.8
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• pp.2577-2583
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• 2011

We have designed a 20-residue hybrid peptide CA(1-8)-MA(1-12) (CAMA) incorporating residues 1-8 of cecropin A (CA) and residues 1-12 of magainin 2 (MA) with high bacterial cell selectivity. CAMA-P2 is an ${\alpha}$-helical antimicrobial peptide designed from a CAMA hybrid peptide and substitution of Gly-Ile-Gly hinge sequence of CAMA to Pro influences the flexibility at central part of CAMA. Based on structure-activity relationships of CAMA peptides, to investigate the effects of the total positive charges on antimicrobial activity of CAMA-P2, the $Ser^{14}{\rightarrow}$Lys analogue (CAMA-syn1) was synthesized. The role of tryptophan at C-terminal ${\alpha}$-helix on its antimicrobial activity as well as synergistic activity was also investigated using $Ser^{14}{\rightarrow}$Lys/$Phe^{18}{\rightarrow}$Trp analogue (CAMA-syn2). Also, we designed CAMA-syn3 by substitution of $Lys^{16}$ located opposite side of substituted $Lys^{14}$ of CAMA-syn1 with Leu residue, resulting in increase of hydrophobicity and amphipathicity of the peptide. All of CAMA-syn analogues showed good antimicrobial activities similar to those of CAMA and CAMA-P2. The CAMA-syn1 and CAMA-syn2 showed low hemolytic activity and cytotoxicity against human keratinocyte Haca-T cells while CAMA-syn3 showed hemolytic activity and cytotoxicity at its MIC value. We then investigated their abilities to act synergistically in combination with the antimicrobial flavonoids and synthetic compounds screened in our laboratory. The results showed that all peptides exhibited synergistic effects with dihydrobinetin, while only CAMA-syn2 exhibited synergistic effects with YKAs3001 against both S. aureus and MRSA, suggesting that Trp residue at C-terminus of CAMA-syn2 may facilitate the polar antibiotic flavonoids and synthetic compounds to permeabilize the membrane. This study will be useful for the development of new antibiotic peptides with potent antimicrobial and synergistic activity but without cytotoxicity.

• Journal of Microbiology and Biotechnology
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• v.7 no.4
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• pp.272-277
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• 1997

In the purification of elaiophylin from a culture of Streptomyces hygroscopicus MCY -846, mono- and di-methyl-elaiophylin were obtained through a O-methylation of the hemiketal hydroxy group of elaiophylin. All the three elaiophylins showed cytotoxicity against several human tumor cell lines and murine cell lines. Elaiophylin and monomethyl-elaiophylin also showed antimicrobial activities against gram-positive bacteria and potent inhibitory effects on the activation of B cells by lipopolysaccharide as well as on the proliferation of mouse splenic lymphocytes stimulated by mitogens but dimethyl-elaiophylin did not. This result indicates that elaiophylin and monomethyl-elaiophylin would be strong immunosuppressants. Furthermore this result revealed an interesting structure-activity relationship suggesting that the lack of symmetry and/or the free OH group at C-11 of elaiophylin might be important in conferring biological activities.

• Journal of Microbiology and Biotechnology
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• v.28 no.3
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• pp.381-390
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• 2018

We have previously derived a novel antimicrobial peptide, LPcin-YK3(YK3), based on lactophoricin and have successfully studied and reported on the relationship between its structure and function. In this study, antimicrobial peptides with improved antimicrobial activity, less cytotoxicity, and shorter length were devised and characterized on the basis of YK3, and named YK5, YK8, and YK11. The peptide design was based on a variety of knowledge, and a total of nine analog peptides consisted of one to three amino acid substitutions and C-terminal deletions. In detail, tryptophan substitution improved the membrane perturbation, lysine substitution increased the net charge, and excessive amphipathicity decreased. The analog peptides were examined for structural characteristics through spectroscopic analytical techniques, and antimicrobial susceptibility tests were used to confirm their activity and safety. We expect that these studies will provide a platform for systematic engineering of new antibiotic peptides and generate libraries of various antibiotic peptides.