Search results for "Structure-Activity relationship"
showing 10 items of 743 documents
Cytotoxic effects of Jay Amin hydroxamic acid (JAHA), a ferrocene-based class I histone deacetylase inhibitor, on triple-negative MDA-MB231 breast ca…
2012
The histone deacetylase inhibitors (HDACis) are a class of chemically heterogeneous anticancer agents of which suberoylanilide hydroxamic acid (SAHA) is a prototypical member. SAHA derivatives may be obtained by three-dimensional manipulation of SAHA aryl cap, such as the incorporation of a ferrocene unit like that present in Jay Amin hydroxamic acid (JAHA) and homo-JAHA [ Spencer , et al. ( 2011 ) ACS Med. Chem. Lett. 2 , 358 - 362 ]. These metal-based SAHA analogues have been tested for their cytotoxic activity toward triple-negative MDA-MB231 breast cancer cells. The results obtained indicate that of the two compounds tested, only JAHA was prominently active on breast cancer cells with a…
Synthesis and biological evaluation of sphingosine kinase 2 inhibitors with anti-inflammatory activity.
2019
The synthesis of inhibitors of SphK2 with novel structural scaffolds is reported. These compounds were designed from a molecular modeling study, in which the molecular interactions stabilizing the different complexes were taken into account. Particularly interesting is that 7‐bromo‐2‐(2‐phenylethyl)‐2,3,4,5‐tetrahydro‐1,4‐epoxynaphtho[1,2‐b]azepine, which is a selective inhibitor of SphK2, does not exert any cytotoxic effects and has a potent anti‐inflammatory effect. It was found to inhibit mononuclear cell adhesion to the dysfunctional endothelium with minimal impact on neutrophil–endothelial cell interactions. The information obtained from our theoretical and experimental study can be us…
Macrolides May Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Entry into Cells: A Quantitative Structure Activity Relationship Study and Exp…
2021
The global pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening the health and economic systems worldwide. Despite the enormous efforts of scientists and clinicians around the world, there is still no drug or vaccine available worldwide for the treatment and prevention of the infection. A rapid strategy for the identification of new treatments is based on repurposing existing clinically approved drugs that show antiviral activity against SARS-CoV-2 infection. In this study, after developing a quantitative structure activity relationship analysis based on molecular topology, several macrolide antibiotics are identified as promising SARS-…
General considerations in the interpretation of I-J genetic restrictions: evidence that the antigen-binding chain of antigen-specific T-suppressor fa…
1987
SUMMARY (CBA × B10)F1 [(H-2k x H-2b)] mice produce two types of antigen-specific T-suppressor factor (TsF), which can be separated by affinity chromatography on anti-I-J monoclonal antibody. After reduction and alkylation, both chains of F1 TsF are required for biological activity. However, the antigen-binding chain (AgBC) of F1 TsFk (AgBCk) is only complemented by I-Jk and likewise for F1 TsFb. In other words, interchain complementation shows the same genetic restriction in interchain complementation in parental and F1 mice. F1 TsF bearing, for example, I-Jk (TsFk), interacts with haptenized ‘antigen-presenting cells’ (‘APC’) of both parental haplotypes, and may be described as showing dua…
A Mechanistic Approach to theIn VivoAnti-Inflammatory Activity of Sesquiterpenoid Compounds Isolated fromInula viscosa
2001
The present study was designed to examine the anti-inflammatory activity of the sesquiterpenoids ilicic acid and inuviscolide, isolated from Inula viscosa, on cell degranulation, leukotriene biosynthesis, neurogenic drive and glucocorticoid-like interactions. Swiss female mice were used to measure the ear oedema induced by phorbol esters or ethyl phenylpropiolate (EPP), and the paw oedema induced by phospholipase A(2) (PLA(2)) or serotonin. Drug treatment consisted of one topically-applied dose in the ear models and a subcutaneous or intraperitoneal injection in the paw models. Quantitative analysis of leukotriene B(4) (LTB(4)) formation was performed on rat peritoneal neutrophils by high p…
(+)-Dehydroabietylamine derivatives target triple-negative breast cancer.
2015
Breast cancer remains the leading cause of cancer-related death among women. The invasive triple-negative subtype is unresponsive to estrogen therapy, and few effective treatments are available. In search of new chemical scaffolds to target this disease, we conducted a phenotypic screen against the human breast carcinoma cell lines MDA-MB-231, MA11, and MCF-7 using terrestrial natural products. Natural products that preferentially inhibited proliferation of triple-negative MDA-MB-231 cells over estrogen receptor-positive cells were further studied; herein we focused on the abietanes. The activity of the abietane carnosol prompted us to generate a focus library from the readily available (+)…
Kaempferol as a dietary anti-inflammatory agent: current therapeutic standing
2020
Inflammation is a physiological response to different pathological, cellular or vascular damages due to physical, chemical or mechanical trauma. It is characterized by pain, redness, heat and swelling. Current natural drugs are carefully chosen as a novel therapeutic strategy for the management of inflammatory diseases. Different phytochemical constituents are present in natural products. These phytochemicals have high efficacy both in vivo and in vitro. Among them, flavonoids occur in many foods, vegetables and herbal medicines and are considered as the most active constituent, having the ability to attenuate inflammation. Kaempferol is a polyphenol that is richly found in fruits, vegetabl…
Benzodiazepines: specific competitors for the binding of L-tryptophan to human serum albumin.
1975
By means of the gel filtration technique, the effect of nine benzo-diazepine derivates on the binding of l-tryptophan to human serum albumin was investigated. Using equimolar tryptophan and benzodiazepine concentrations, all benzodiazepines with binding constants higher than 104 (M−1), displace l-tryptophan from its binding site to a high degree. The mechanism of the displacement was characterized as a competition for a common binding site. Some of the benzodiazepines displace l-tryptophan to a greater extent than salicylic acid. The benzodiazepines and tryptophan are the only substances known with a high degree of stereospecific binding to human serum albumin. This study shows that there i…
Synthesis, biological evaluation, and structure-activity relationship study of novel cytotoxic aza-caffeic acid derivatives.
2010
Abstract Three series of aza-caffeic acid derivatives with different linkers were designed and synthesized. Each of the synthesized derivatives was then used in cytotoxicity screening on either 8 or 12 human cancer cell lines. The structure–activity relationships on three structural regions A, B, and C are analyzed in detail, indicating that a nine bond linker B, containing a piperazine unit, is the most favorable linker leading to the generation of molecules with potent cytotoxicities. Compound ( E )-1-(4-(3,4-dichlorobenzyl)piperazin-1-yl)-3-(4-(4-ethoxybenzyloxy)-3,5-dimethoxyphenyl)prop-2-en-1-one ( 80 ) exhibited the most significant and selective cytotoxicity to KB, BEL7404, K562, and…
Prediction of quinolone activity against Mycobacterium avium by molecular topology and virtual computational screening.
2000
ABSTRACT We conducted a quantitative structure-activity relationship study using a database of 158 quinolones previously tested against Mycobacterium avium-M. intracellulare complex in order to develop a model capable of predicting the activity of new quinolones against the M. avium-M. intracellulare complex in vitro. Topological indices were used as structural descriptors and were related to anti- M. avium-M. intracellulare complex activity by using the linear discriminant analysis (LDA) statistical technique. The discriminant equation thus obtained correctly classified 137 of the 158 quinolones, including 37 of a test group of 44 randomly chosen compounds. This model was then applied to 2…