Medicinal Chemistry - Volume 2, Issue 4, 2006

Steroidogenic enzyme type 3 17β-hydroxysteroid dehydrogenase (17β-HSD) is an important therapeutic target for androgen-sensitive diseases. This enzyme selectively reduces the C17 ketone of 4-androstene-3,17-dione (Δ4-dione), thus producing testosterone (T) using NADPH as cofactor. Our group previously synthesized hybrid (estradiol/adenosine) inhibitors that successfully inhibit the biosynthesis of the potent estrogen Read More

The trypsin-like serine protease factor Xa (fXa) is located at the convergence point of the intrinsic and extrinsic coagulation cascade, and therefore has emerged as an attractive target for the design of novel anticoagulants. During the development of substrate-analogue urokinase inhibitors we have found that the protection of the P3-DSer side chain leads to a scaffold of potent fXa inhibitors with the general structure R1-SO2-D Read More

A lanosterol 14α-demethylase inhibitors of chromene series were subjected to classical quantitative structural activity relationship studies. Apart from the indicator variables encoding for different group contribution, there are various physico-chemical descriptors like steric, thermodynamic and electronic parameters, which were applied to explore the structural requirements for inhibition of enzyme. Multiple linear regressio Read More

Bisdioxopiperazines, including ICRF-154 and razoxane (ICRF-159, Raz), are a family of anticancer agents developed in the UK, specifically targeting neoplastic metastases. Two other bisdioxopiperazine derivatives, probimane (Pro) and MST-16, were synthesized at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. In order to determine the similarities and differences between these ag Read More

A new benzophenone O-glucoside neoannulatophenonoside (1) together with the known pinocembrin-7-Oglucoside were isolated from the aerial parts of Hyperium annulatum Moris (Guttiferae). The former was identified as 3',5',6-trihydroxy-4-methoxybenzophenone-2-O- β-D-glucopyranoside by means of chemical and physical evidence. The cytoprotective effects of the new compound together with the previously isolated fro Read More

The fundamental physico-chemical parameters of sertraline, a potent selective serotonin reuptake inhibitor and reference compound in the development of new antidepressive agents, were determined. The thermodynamic solubility of the hydrochloride salt (S = 4.24 ± 0.02 mg/ml) and the free base form (S ≈ 0.002 mg/ml) was measured by the saturation shake-flask method. The co-solvent technique in methanol/water Read More

Cyclosporin-A (CsA) is often used in the treatment of nephrotic syndrome. The effectiveness of CsA and the value of C2 blood levels in the treatment of nephrotic syndrome, due to various glomerular diseases, were studied. Forty-two nephrotic patients (M/F 21/21), with well-preserved renal function (creatinine clearance 87± 20ml/min) were included in the study. The original diagnoses were minimal change disease (MC Read More

The surface loops of proteins and active peptides are implicated in the activation of biological responses upon recognition by enzymes and receptors. Obviously, it is of interest to investigate these loops as potential leads for drug discovery. Currently, there is an urgent need for novel, general, and conformationally definite cyclic peptidomimetic scaffolds capable to mimic small portions of the protein surface. In this res Read More

Activation by human cytochrome P450 1A2 (hCYP1A2) of heterocyclic amines is assumed to trigger of a number of carcinogenic processes. In this work, a group of natural inhibitors of human cytochrome P450 1A2 reported in literature has been theoretically analysed. These consist of flavone hydroxylated derivatives, natural compounds that exist in plants and associated products. Different theoretical/computational tools were Read More

Acting as a redox switch, folic acid (1) might be a promising iron modulator to protect cellular machinery against oxidative stress and iron overload. The vitamin 1 can directly control the iron concentration by oxidizing it even if present in chelated forms. In addition, during its role as a reducing agent for the biologically relevant reactive oxygen species (ROS), it furnishes 6-formyl pterin. This folate-derived intermediate possesses Read More

Antituberculosis activity of several 5-(4-aminophenyl)-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones (1- 9) and their thiourea derivatives (10-31) were screened for their antimycobacterial activities against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. Of the synthesized compounds, 10-12, 30 were the most active derivatives exhibiting more than 90 % inhibition of mycobacterial growth at Read More

Introduction: Acute pancreatitis is a disease involving pro-inflammatory mediators. Two complex and multifactorial pathogenetic ways lead to edematous or necrotizing pancreatitis. The course of the disease is thought to be the consequence of an acute inflammatory response. AIM: The authors examined the impact of Escherichia coli LPS on the acute cerulein pancreatitis in rats. Methods: The study was performed on ra Read More

Retinoids have been investigated for their therapeutic potential for the past 3 decades. They have a reputation for being both beneficial in the treatment of several diseases and detrimental due to toxic and/or teratogenic side effects. The purpose of this review is to highlight retinoids that are currently used in the clinic. We also discuss their mechanisms of action and research strategies to develop new and safer retinoid-b Read More