Merck
  • Home
  • Search Results
  • Cellular apoptosis and cytotoxicity of phenolic compounds: a quantitative structure-activity relationship study.

Cellular apoptosis and cytotoxicity of phenolic compounds: a quantitative structure-activity relationship study.

Journal of medicinal chemistry (2005-11-11)
Cynthia D Selassie, Sanjay Kapur, Rajeshwar P Verma, Melissa Rosario
ABSTRACT

In this comprehensive study on the caspase-mediated apoptosis-inducing effect of 51 substituted phenols in a murine leukemia cell line (L1210), we determined the concentrations needed to induce caspase activity by 50% (I50) and utilized these data to develop the following quantitative structure-activity relationship (QSAR) model: log 1/I50 = 1.06 B5(2) + 0.33 B5(3) - 0.18pi(2,4) - 0.92. B5(3) and B5(2) represent steric terms, while pi(2,4) represents the hydrophobic character of the substituents on the ring. The strong dependence of caspase-mediated apoptosis on mostly steric parameters suggests that the process is a receptor-mediated interaction with caspases or mitochondrial proteins being the likely targets. Conversely, cytotoxicity studies of 65 electron-releasing phenols in the L1210 cell line led to the development of the following equation: log 1/ID50 = -1.39sigma+ - 0.28 B5(2,6) + 0.16 log P - 0.58I(2) - 1.04I(1) + 3.90. The low coefficient with log P may pertain to cellular transport that may be enhanced by a modest increase in overall hydrophobicity, while the presence of sigma+ is consistent with the suggestion that radical stabilization is of prime importance in the case of electron-releasing substituents. On the other hand, the QSAR for the interactions of 27 electron-attracting phenols in L1210 cells, log 1/ID50 = 0.56 log P - 0.30 B5(2) + 2.79, suggests that hydrophobicity, as represented by log P is of critical importance. Similar cytotoxicity patterns are observed in other mammalian cell lines such as HL-60, MCF-7, CCRF-CEM, and CEM/VLB. The significant differences between the cytotoxicity and apoptosis QSAR for electron-releasing phenols suggest that cytotoxicity involves minimal apoptosis in most of these substituted monophenols.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2,6-二--丁基-4-甲基苯酚, ≥99.0% (GC), powder
Sigma-Aldrich
对苯二酚, ReagentPlus®, ≥99%
Sigma-Aldrich
苯酚 溶液, Equilibrated with 10 mM Tris HCl, pH 8.0, 1 mM EDTA, BioReagent, for molecular biology
Sigma-Aldrich
苯酚, puriss. p.a., ACS reagent, reag. Ph. Eur., 99.0-100.5%
Sigma-Aldrich
β-雌二醇, BioReagent, powder, suitable for cell culture
Sigma-Aldrich
丁羟甲苯, ≥99%, FCC, FG
Sigma-Aldrich
β-雌二醇, ≥98%
Sigma-Aldrich
3',5'-二甲氧基-4'-羟基苯乙酮, 97%
Sigma-Aldrich
苯酚, for molecular biology
Supelco
双酚 A, ≥99%
Sigma-Aldrich
对乙酰氨基酚, BioXtra, ≥99.0%
Sigma-Aldrich
液状苯酚, ≥89.0%
Sigma-Aldrich
苯酚, BioXtra, ≥99.5% (GC)
Sigma-Aldrich
苯酚 溶液, Saturated with 0.1 M citrate buffer, pH 4.3 ± 0.2, BioReagent, for molecular biology
Sigma-Aldrich
Resorcinol, ACS reagent, ≥99.0%
Supelco
3,5-二叔丁基-4-羟基甲苯 (BHT), analytical standard
Sigma-Aldrich
苯酚, ≥99%
Sigma-Aldrich
邻苯二酚, ReagentPlus®, ≥99%
Sigma-Aldrich
对乙酰氨基酚, meets USP testing specifications, 98.0-102.0%, powder
Sigma-Aldrich
愈创木酚, oxidation indicator
Sigma-Aldrich
对苯二酚, ReagentPlus®, 99%
Sigma-Aldrich
对羟基苯甲醛, 98%
Sigma-Aldrich
愈创木酚, natural, ≥99%, FG
Sigma-Aldrich
邻苯二酚, ≥99%
Sigma-Aldrich
对乙酰氨基酚, analytical standard
Sigma-Aldrich
Resorcinol, ReagentPlus®, 99%
Sigma-Aldrich
4-氯苯酚, ≥99%
Sigma-Aldrich
:2,4-二丁基苯酚, 99%
Sigma-Aldrich
4-叔丁基苯酚, 99%
Sigma-Aldrich
苯酚, contains hypophosphorous as stabilizer, loose crystals, ACS reagent, ≥99.0%