Medicinal Chemistry - Volume 8, Issue 5, 2012

The Editorial Board wishes to dedicate this issue of Medicinal Chemistry to the Editor-in-Chief of the journal, Prof. Dr. Atta-ur-Rahman, FRS, on his 70th birthday. The Editorial Board acknowledges the tremendous achievements of Prof. Rahman in the fields of Organic Chemistry in general and on bioactive natural products in particular. Prof. Rahman’s honors include: the first scientist from the Muslim world to have won the pres Read More

A series of 1,3-oxathiolane-based nucleoside analogs 5-methyl substituted was synthesized and tested as potential antiviral agents. Structural characterization and C2-C4 / C2-C5 relative stereochemistry assignments were performed by NMR experiments. All tested isomers were found to be inactive and cytotoxic.

The synthesis of twenty seven novel pyrazole derivatives bearing aryl substituted groups at positions 1 and 3 of the pyrazole structural motif and various functional groups at position 4 is presented. The critical step for their synthesis is the TCT/DMF promoted cyclization of the corresponding hydrazine precursors, which provided the desired pyrazole skeleton. The anticancer properties of the novel pyrazole derivatives were ev Read More

Despite numerous synthetic efforts and extensive SAR studies on paclitaxel analogs, little work has been devoted to derive SAR of the C-1 hydroxy group. Up to now, 1-deoxypaclitaxel has only been reported to be isolated from the Chinese yew, Taxus mairei (Taxaceae). However, the isolation from natural sources does not solve the availability problem due to the reported low yield of isolation. Also, only several analogues of thi Read More

Leflunomide is an immunomodulating drug that has been used clinically for the treatment of rheumatoid arthritis and other immune system disorders. As a continuation of our previous work, four novel analogues of leflunomide (6a, 6b, 7a and 7b) were synthesized; here, an imidazolyl group has replaced the isoxazolyl moiety, while the 4- trifluoromethylphenyl group has been retained. These analogues were synthesize Read More

All-trans-retinoic acid reverses malignant cell growth and induces cell differentiation and apoptosis. Poor aqueous solubility and uncertain bioavailability are the limiting factors for using all-trans-retinoic acid for tumor therapy. The objective of present study was to encapsulate the hydrophobic drug all-trans-retinoic acid in the polymer poly (lactide-coglycolide). The encapsulation was expected to improve the bioava Read More

This study critically examines the role of conceptual DFT descriptors and docking scores on a diverse set of 156 inhibitors of HIV proteases. Five QSAR models were developed on the basis of available experimental IC50 values (HIV-I and HIV-IIIB infected MT4 and CEMSS cells and HIV-I infected C8166 cells) and sixth QSAR model was generated by combining the inhibitors of all five models. B3LYP/6-31G(d) optimizations Read More

Two novel groups of hexapeptide inhibitors for NS3 serine protease of the hepatitis C virus (HCV) are designed. The hexapeptide is an amino acid sequence of NS5A/NS5B substrate (Glu-Asp-Val-Val-Cys-Cys). In the first group, the hexapeptide binds to a cellulose monomer at the positions 2, 3 or 6 while in the second group, the hexapeptide binds to a cellulose dimmer at the positions 2, 3, 6, 2', 3'or 6'. Molecular modeling semie Read More

In order to discover compounds with superior anti-human immunodeficiency virus type 1 (HIV-1) activity, 9 new indolyl glyoxamide derivatives (3a-i) were synthesized and preliminarily evaluated as HIV-1 inhibitors in vitro. Among all the derivatives, especially compounds 3e and 3h showed the potent anti-HIV-1 activity with EC50 values of 6.83 and 4.35 μg/mL, and TI values of >27.15 and 49.45, respectively. It demonstrated tha Read More

Thiazolidinedione (TZD) derivatives are the novel class of oral antidiabetic drugs which are selective agonist for the nuclear PPAR γ that enhances the transcription of several insulin responsive genes but TZDs are known to cause weight gain, hepatotoxicity and fluid retention. So a new series of coumarin coupled thiazolidinedione derivatives and its bioisosters (oxazolidinedione and imidazolidinedione) were synthesized by Knoeve Read More

A series of metronidazole ester derivatives 1-34 has been synthesized with the aim of developing new leads with antiglycation activity. The in vitro evaluation of antiglycation potential of 1-34 showed that the ester derivatives 28, 16, and 3 have IC50 values 218.97 ± 2.5, 245.3 ± 5.1, and 278.6 ± 0.8 μM, respectively, comparable to the standard agent, rutin (IC50 = 294.5 ± 1.50 μM). The study identifies a new class of potent anti Read More

In silico based QSAR and pharmacophore analyses of a series of piperidine derivatives were performed in order to investigate the structural features of the derivatives responsible for FTase inhibitory activity. The results derived from the QSAR analysis show that the FTase inhibitory activity mediated by the vdW surface area features such as partial charge (PEOE_VSA and Q_VSA) and v_surf (hydrophobic integy moment) of t Read More

Eight aromatic amino acid derivatives (9a-9h) as gastrin-releasing peptide receptor (GRPR) antagonists were designed and synthesized. For the design, the tertiary structure of GRPR was predicted by blast searching in the premise of 1u19 protein as the template. Eight target compounds were docked into the binding pocket to investigate their possible binding interactions. Their anti-itch activities were tested by intrathecal Read More

Indan derivatives, namely, 5-(5',6'-dichloroindan-1'-yl)-tetrazole (12a) and 5-(5',6'-dichloroindan-1'-yl)- methyltetrazole (12b), were synthesized conveniently from 5,6-dichloroindan-1-carboxylic acid (9a) and 5,6- dichloroindan-1-acetic acid (9b), respectively, as potential analgesic and anti-inflammatory agents. The analgesic and anti-inflammatory properties of 9a, 9b, 12a and 12b were evaluated by the acetic acid induced Read More

The influence of a number of usnic acid derivatives on auto(polyADP-ribosyl)ation catalyzed by PARP1 and DNA synthesis catalyzed by DNA polymerase β was studied. The derivatives of usnic acid containing aromatic substituents were shown to be moderate inhibitors of PARP1. The presence of both usnic acid tricyclic structure and aromatic substituent at any position of the molecule is a key factor for the inhibitory a Read More

In the present study, three dimensional quantitative structure activity relationship (3D QSAR) models using 3D Pharmacophore, CoMFA and CoMSIA approaches were developed for a series of phenyl alkyl ketone derivatives as PDE4 receptor antagonists. An ideal 3D QSAR pharmacophore model was developed and validated using external test set, Fischer's randomization method and decoy set screening. The top scoring four feat Read More

RTKs - Receptor Tyrosine Kinases are the key regulators for cellular function and any abnormalities in the signaling of such leads to cancer. Mutations that result in the constitutive activation of this receptor result in Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia. Pharmacophore mapping, a well-established method is used to build up 3D QSAR model from two classes of compounds viz. 2-acylamin Read More

A series of novel Ligustrazinyl acylguanidines was designed, synthesized and evaluated for their protective effect on injured vascular endothelial cell (ECV-304). The preliminary results demonstrated that some compounds possessed more potent activities than that of Ligustrazine in stimulating replication of the injured endothelial cell. Among the active compounds, compounds 8b, 8f and 8l displayed remarkable antioxidative act Read More

As one of the main active component of protopanaxdiol type ginsenosides, ginsenoside Rb3 is rarely reported in the treatment of diabetes. The anti-diabetic activity of ginsenoside Rb3 was investigated in a model of alloxan-induced diabetic mice in the present study. The physiological parameter such as fasting blood glucose level, oral glucose tolerance, body weight, food intake and water intake were measured. Gluco Read More

In order to predict the antioxidant activity of 7 polycyclic lactams, a two dimensional quantitative-structure activity relationships (2D-QSAR) study based on a 5-descriptor model was performed. The synthetic compounds built from a condensed lactam scaffold were screened for their abilities to inhibit the autoxidation of pyrogallol, a superoxide anion radical-dependent process. The ketone 2 (8,9-dihydro-7H-benzo[de]pyrrolo[1,2- Read More