Abstract：
:A new analysis of the quantitative structure-activity relationship (QSAR) of the antitumor activity of anilinoacridines against L1210 leukemia in mice and mouse toxicity is reported. QSAR have also been derived for the inhibitory activity of the anilinoacridines with tumor cells and their binding to DNA. These results are compared with reactivity with simple nucleophiles. The comparative analysis shows the importance of electron releasing substituents (in general negative coefficients with the Hammett parameter sigma+) throughout the various systems and the complete lack of hydrophobic interactions from DNA to cells to mice. The presence of steric terms suggests that a protein receptor is involved. The study shows that QSAR has an important role to play in improving the efficiency in the design of bioactive compounds and that care must be taken in the design of a set of congeners so that the necessary parameters are available to do the QSAR analysis. Our study illustrates the value of comparative QSAR in generalizing our understanding of chemical-biological interactions.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Gao H,Denny WA,Garg R,Hansch Cdoi
10.1016/s0009-2797(98)00085-4subject
Has Abstractpub_date
1998-11-27 00:00:00pages
157-80issue
3eissn
0009-2797issn
1872-7786pii
S0009279798000854journal_volume
116pub_type
杂志文章abstract：:Styrene oxide was reacted with deoxynucleosides and DNA in aqueous buffer at pH 7.4. The products were purified by HPLC, characterized by UV spectroscopy and by chemical ionization mass spectrometry. The main products identified were 7-alkyl-, N2-alkyl- and O6-alkyldeoxyguanosine, 1-alkyl-, and N6-alkyldeoxyadenosine,...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(86)90055-4
更新日期：1986-12-01 00:00:00
abstract：:The administration of the placental hormone human chorionic gonadotrophin (HCG) to 50-day-old virgin Sprague--Dawley rats has been shown to reduce the incidence of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary cancer. We now report from studies using rat mammary epithelial cells in culture that the anti-carcin...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(85)80117-4
更新日期：1985-10-01 00:00:00
abstract：:Intracellular calcium (Ca(2+)i) overload induced by chronic hypoxia alters Ca(2+)i homeostasis, which plays an important role on mediating myocardial injury. We tested the hypothesis that treatment with trimetazidine (TMZ) would improve Ca(2+)i handling in hypoxic myocardial injury. Cardiomyocytes isolated from neonat...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.04.022
更新日期：2015-07-05 00:00:00
abstract：:Tumor angiogenesis and PI3K/Akt/mTOR pathway are two major molecular objectives for the treatment and management of breast cancer. Here we first time report the molecular mechanism of a marine sponge alkaloid derivative 4-chloro fascapysin (4-CF) for its anticancer and antiangiogenesis potential. It simultaneously tar...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.07.017
更新日期：2017-09-25 00:00:00
abstract：:AKR1B10 is a human-type aldo-keto reductase. The up-regulation of AKR1B10 has been associated with various cancers including non-small cell lung carcinoma, viral and bacterial infections, and skin diseases. However, the mechanisms underlying AKR1B10 gene regulation are not fully understood. We previously indicated the...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.02.008
更新日期：2017-10-01 00:00:00
abstract：:Benzene-induced hematopoietic toxicity is an aryl hydrocarbon receptor (AhR)-related adverse effect that is not exhibited in AhR-knockout (KO) mice. In the hematopoietic system, the steady-state expression of AhRs is limited in the hematopoietic progenitor cells; thus, a hierarchical hematopoietic impairment starts fr...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2009.12.022
更新日期：2010-03-19 00:00:00
abstract：:Misonidazole is readily reduced by zinc dust in aqueous solution in the presence of ammonium chloride. High pressure liquid chromatographic (HPLC) separation of the reduction mixture revealed the presence of three products. These were identified as the hydroxylamine, amine and the hydrazo derivative of misonidazole. T...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(81)90016-8
更新日期：1981-08-01 00:00:00
abstract：:Two homogenous fractions of hepatic metallothioneins ((Cd,Zn) MT-1 and (Cd,Zn) MT-2) and renal metal binding proteins ((Bi,Cu) BP-1 and (Bi,Cu) BP-2) were isolated from rats exposed to heavy metals and specific antisera to them were produced in rabbits. These antisera were tested by immunodiffusion and immunoelectroph...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(80)90048-4
更新日期：1980-12-01 00:00:00
abstract：:Neutrophils from asymptomatic HIV-infected patients have an increased Nitroblue tetrazolium (NBT) reduction, that is an increased production of oxygen radicals. Plasma from these patients can activate normal neutrophils to an increased NBT-reduction and the neutrophil activating factor thus seems to be mainly plasma b...
journal_title：Chemico-biological interactions
pub_type： 杂志文章,评审
doi：10.1016/0009-2797(94)90034-5
更新日期：1994-06-01 00:00:00
abstract：:The mechanism of mitochondrial dysfunction and toxicity induced by the tropolones, beta-thujaplicin (4-isopropyl tropolone), tropolone and tropone, has been studied in freshly isolated rat hepatocytes. Incubation of hepatocytes with beta-thujaplicin (1-4 mM) elicited a concentration and time-dependent cell killing. Th...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(98)00078-7
更新日期：1998-11-06 00:00:00
abstract：:Human foreskin cell cultures in scheduled DNA synthesis (S phase) of the cell cycle were exposed to UV irradiation at a dose of 10 J . m-1 in the presence of insulin. These treated cell populations, when selectively passaged in a high amino acid supplemented complete growth medium (CM) after 20 Dulbecco's phosphate bu...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(81)90028-4
更新日期：1981-07-01 00:00:00
abstract：:Methylglyoxal (2-oxopropanal) is a cytotoxic compound that can be formed endogenously as a by-product of glycolytic pathway; so its concentration is expected to increase when glycolysis activity increases such as during embryo development. In this work we study the effect of exogenous methylglyoxal on development and ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(98)00048-9
更新日期：1998-07-24 00:00:00
abstract：:Parthenolide (PTL), a well-known sesquiterpene lactone of natural origin with α,β-unsaturated carbonyl structure, has proven to show promising anti-cancer properties. In this report, anti-proliferative potential of two synthetic methyleneisoxazolidin-5-ones, MZ-6 and MZ-14, with the same structural motif, has been inv...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.01.011
更新日期：2016-03-25 00:00:00
abstract：:Despite the advances in early detection and targeted therapies, chemotherapy is still of vital importance in breast cancer treatment. However, development of drug resistance and serious side effects limits their usage. Thus, there is an urgent need for safer and more effective agents against breast cancer. We have pre...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.12.010
更新日期：2017-02-01 00:00:00
abstract：:The 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethene (DDT) metabolic intermediate 1-chloro-2,2-bis(p-chlorophenyl)ethene (DDMU) is partially metabolized in vivo by mice to 2-hydroxy-2,2-bis(p-chlorophenyl)acetic acid (alpha OH-DDA) and other metabolites which are excreted in urine. The subsequent DDT metabolic intermedia...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(81)90140-x
更新日期：1981-05-01 00:00:00
abstract：:Cucurbitacin E (CuE) is a triterpenoid with potent anticancer activities while the underlying mechanisms remain elusive. In the present study, the anticancer effects of CuE on 95D lung cancer cells were investigated. CuE decreased cell viability, inhibited colony formation, and increased reactive oxygen species (ROS) ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2016.04.028
更新日期：2016-06-25 00:00:00
abstract：:Resistance to chemotherapeutic agent is a major cause of treatment failure in patients with cancer. In many cases, the primaly mechanism leading to a multidrug-resistant phenotype is the plasma-membrane localized overexpression of drug efflux transporters, such as P-glycoprotein. However, acidic intracellular organell...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(01)00157-0
更新日期：2001-07-31 00:00:00
abstract：:Arginase is a therapeutic enzyme for arginine-auxotrophic cancers but their low anticancer activity, less proteolytic tolerance and shorter serum half-life are the major shortcomings. In this study, arginase from Pseudomonas aeruginosa IH2 was purified to homogeneity and estimated as 75 kDa on native-PAGE and 37 kDa o...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.07.001
更新日期：2017-08-25 00:00:00
abstract：:This study examines the relationship between cell progress into the state of unbalanced growth, hydrolytic enzyme activities and cell survival during the exposure of L5178Y cells to hydroxyurea (HU), excess thymidine (dThR), hydroxyurea with excess of four deoxyribonucleosides (dNR) or excess dTHR with deoxycytidine (...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(86)90006-2
更新日期：1986-03-01 00:00:00
abstract：:(1) Subcutaneous or intra-abdominal injections of 8 mg of HgCl2/100 g body weight markedly depressed hepatic fatty acid synthetase activity of chicks at 1 h post-injection. The depression occurred despite the fact that the chicks continued to eat up until the time they were killed. Under these same conditions, the hep...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(75)90003-4
更新日期：1975-11-01 00:00:00
abstract：:The change in the expression of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities in neoplastic colon and lung prompted us to study the possible effect of cancer on the expression of cholinesterases (ChEs) in kidney. Samples of papillary renal cell carcinoma (pRCC), conventional RCC (cRCC), chro...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2008.04.003
更新日期：2008-09-25 00:00:00
abstract：:Within the alpha/beta hydrolase fold superfamily of proteins, the COesterase group (carboxylesterase type B, block C, cholinesterases …) diverged from the other groups through simultaneous integration of an N-terminal, first disulfide bond and a significant increase in the protein mean size. This first disulfide bond ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.05.016
更新日期：2019-08-01 00:00:00
abstract：:Mammalian steroid 5β-reductases belong to the Aldo-Keto Reductase 1D sub-family and are essential for the formation of A-ring 5β-reduced steroids. Steroid 5β-reduction is required for the biosynthesis of bile-acids and the metabolism of all steroid hormones that contain a Δ4-3-ketosteroid functionally to yield the 5β-...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.03.025
更新日期：2019-05-25 00:00:00
abstract：:Diabetes mellitus causes derangement of carbohydrate, protein and lipid metabolism which eventually leads to a number of secondary complications. Terminalia bellerica is widely used in Indian medicine to treat various diseases including diabetes. The present study was carried out to isolate and identify the putative a...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2010.11.005
更新日期：2011-01-15 00:00:00
abstract：:Liquid-holding recovery and rejoining of gamma-radiation-induced DNA single-strand scissions in Escherichia coli could be effectively inhibited by procaine hydrochloride at the concentration of 20 mM. At this concentration, the drug also reversibly altered cellular permeability barrier as evidenced from the uptake of ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(75)90097-6
更新日期：1975-09-01 00:00:00
abstract：:In humans, the aldehyde dehydrogenase superfamily consists of 19 isoenzymes which mostly catalyze the NAD(P)(+)-dependent oxidation of aldehydes. Many of these isoenzymes have overlapping substrate specificities and therefore their potential physiological functions may overlap. Thus the development of new isoenzyme-se...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.12.038
更新日期：2015-06-05 00:00:00
abstract：:Human carbonyl reductases 1 and 3 (CBR1 and CBR3) are monomeric NADPH-dependent enzymes of the short-chain dehydrogenase/reductase superfamily. Despite 72% identity in primary structure they exhibit substantial differences in substrate specificity. Recently, the endogenous low molecular weight S-nitrosothiol S-nitroso...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2011.01.016
更新日期：2011-05-30 00:00:00
abstract：:tert-Butylhydroquinone (BHQ), an antioxidant used as a food additive, exhibits an anticancer effect at low doses, but is carcinogenic in rodents at high doses. BHQ is metabolized into cytotoxic tert-butylquinone (TBQ), which is further converted to 6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one (TBEH) through 6-t...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.09.023
更新日期：2015-06-05 00:00:00
abstract：:The reduction of hexavalent chromium (Cr(VI] by rat liver microsomes was studied. With 15-120 microM Na2CrO4 microsomes (0.5 mg protein/ml) effectively reduced Cr(VI) in the presence of NADPH provided anaerobic conditions. Phenobarbital (PB) and Aroclor 1254 (PCB) pretreatment increased microsomal Cr(VI) reduction whi...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(89)90076-8
更新日期：1989-01-01 00:00:00
abstract：:Our laboratory has been routinely using suspended and cultured human hepatocytes for predicting drug metabolism and enzyme induction by drug candidates to aid drug discovery. Increasing limitation and irregular availability of human tissue has indicated the need for maximizing the use of this valuable resource. Cryopr...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(99)00090-3
更新日期：1999-06-01 00:00:00
