Medicinal Chemistry - Volume 8, Issue 2, 2012

Magnetic resonance imaging (MRI) is presently the method of choice for detection of brain tumors. However, MRI alone is not conclusive. As the commonly used contrast agents do not bind to the cells and are not taken up into the cells, they generally do accumulate in regions where the blood-brain-barrier is disrupted. While this can be brain tumors (WHO grade II-III and above), it can also be inflammations. A cell-directe Read More

Within the United States, primary brain tumors account for 20 to 25 percent of all pediatric cancers. Chemotherapy utilizing a nitrosourea, notably semustine (MeCCNU) and carmustine (BCNU), has shown significant success in the treatment of tumors found in the central nervous system. In silico optimization of molecular properties by substituent substitution that is followed by pattern recognition analysis is utilized in this stu Read More

As a continuation to our previous work in developing anticancer agents, eighteen symmetrical biphenyl derivatives structurally related to taspine were synthesized and evaluated in vitro and in vivo. All the compounds were prepared with varied substitutions in the phenyl ring of aniline moiety. The cytotoxicity and anticancer activity of biphenyls was evaluated against various human tumor and normal cell line. Antiproliferative a Read More

Most of cancer chemotherapeutics and chemopreventives exert their effects by triggering apoptotic cell death. In this study, novel benzimidazole and benzothiazole derivatives have been synthesized to investigate their effects on HepG2 liver cancer cell lines after initial screening study. A dose response curve was constructed and the most active derivatives were further studied for apoptotic analysis. Six active benzimidazole de Read More

We have previously found that the dithiocarbamate derivatives of quinazolin-4(3H)-one could act as cytotoxic agents against a panel of human tumor cell lines. To investigate the contribution of dithiocarbamate moiety to the cytotoxic activity, three series of novel quinazolin-4(3H)-one derivatives bearing thiocarbamate, thiourea or Nmethyldithiocarbamate side chains were synthesized and tested for their cytotoxic acti Read More

Through their reactive oxygen species (ROS) producing function, NADPH oxidase (NOX) enzymes have been linked to several oxidative stress related diseases. In our recently published paper [1] we have already shown the NOX4 inhibitory effect of diverse, molecule sub-libraries and their biological importance. We also presented our work connected to potential anti-tumour molecules and the relationship between their biol Read More

In an effort to discover new candidates with improved antimicrobial activities, we synthesized and studied invitro antimicrobial activities of various series of 3-((thiophen-2-yl)-ethyl)-2-(styryl)-quinazolin-4(3H)-one (3a-3g) and N1-(substituted aryl)-N3-[3-((3,4-dimethoxy phenyl-2-yl)-ethyl)-4(3H)-quinazolone-2-yl]-acetonyl semicarbazides (7a-7j) with an intent to overcome multiple drug resistance to the pathogenic strains and to r Read More

Conjugates between suramin, a polyanionic naphthalene sulfonate derivative, and nucleoside reverse transcriptase inhibitors (NRTIs), 3'-azido-2',3'-dideoxythymidine (AZT) and 3'-fluoro-2',3'-dideoxythymidine (FLT), were designed to create an antiretroviral with multiple mechanisms of action that could be developed as an anti-HIV topical microbicide candidate. The anti-HIV activity of these conjugates was compared with that Read More

Comparative molecular field analysis (CoMFA) is a widely used 3D-QSAR method by which we can investigate the potential relation between biological activity of compounds and their structural features. In this study, a new application of this approach is presented by combining the molecular modeling with a new developed pharmacophore model specific to CYP1A2 active site. During constructing the model, we use Read More

CYP2E1, as a member of the cytochrome P450s (CYPs) super-family, is in charge of six percent drug metabolism involving a diversity of drugs distinct in structures and chemical properties, such as alcohols, monocyclic compounds (e.g., acetaminophen, benzene, p-nitrophenol), bicyclic heterocycles (e.g., coumarin, caffeine) and even fatty acids. The aromatic molecules form a vital species catalyzed by CYP2E1. To invest Read More

Arsenic compounds have shown medical usefulness since they proved to be effective in causing complete remission of acute promyelocytic leukemia. In this work we obtained a fluorescently labeled arsenic compound that can be used with current fluorescence techniques for basic and applied research, focused on arsenic-induced apoptosis studies. This compound is an arsanilic acid bearing a covalently linked FITC that Read More

A comparative analysis of stereo-electronic properties of five cholinesterase reactivators (pralidoxime (2- PAM), trimedoxime, obidoxime, HI-6, and HLo-7) and six “K-oximes” was performed to assess their roles in reactivating OP-inhibited phosphorylated serine residue of mouse AChE. Quantum mechanical (QM) calculations starting from semiempirical to ab initio levels were sequentially performed with hierarchical basis sets to o Read More

Ketamine (2-o-chlorophenyl-2-methylaminocyclohexan, CAS 1867-66-9, CI-581, Ketalar, I), a potent derivative of Phencyclidine (1-[1-phenylcyclohexyl] piperidine, CAS 956-90-1, PCP, II), and many of its analogues have shown anesthetic and analgesic effects. In this research, new derivatives of I, (2-[p-methoxybenzylamino]-2-[p-methoxyphenyl] cyclohexanone, ket-OCH3, III), (2-[p-methylbenzylamino]-2-[p-methox Read More

Malaria, one of the most widespread and deadly infectious diseases continues to kill over 1 million people every year. This scenario is getting even worse as P. falciparum develops resistance to existing drugs. Thus, there is an imperative need for novel and more effective antimalarials. Farnesyltransferase (PFT) appears to be a promising therapeutic target to development of antimalarial drugs and many analogs of PFT i Read More

A series of hydroxyethylamines has been synthesized from the reaction of (2S,3S )Boc-phenylalanine epoxide with alkyl amines in good yields and evaluated for their in vivo antimalarial activity in mice. Compound 4g presented better activity then the reference artesunate in percentage of inhibition of parasitemia in treated P. berghei-infected mice and compare to the activity of artesunate in the survival of mice 14 days aft Read More

Four novel drug designs for the treatment of Mycobacterium tuberculosis are analyzed and shown to prevent the growth and proliferation of this dangerous bacteria. All four agents, designated A, B, C, and D, are hydrazide type compounds, where D has three hydrazide functional groups. Agents B and C have a halogenated aromatic ring substituent, while A contains a pyridine ring. Pharmaceutical properties such as Log P, Read More

A set of 2-benzylsulfanyl derivatives of benzothiazole was synthesized and evaluated for antimicrobial and cytotoxic activities. The biological screening on antimicrobial activity against a panel of Gram-positive and Gramnegative bacteria, yeasts and fungi identified benzylsulfanyl derivatives of benzothiazole as selective inhibitors of mycobacteria. The lead compounds in the set, dinitro derivatives exhibited significa Read More

Recent studies indicated that andrographolide was a potential antihyperlipidaemic therapeutic agent. In the paper, the synthesis of a series of andrographolide derivatives was described and their antihyperlipidaemic activities were evaluated in vivo. As compared with TG, TC, HDL-C and LDL-C concentrations, some of the derivatives exhibited better antihyperlipidaemic effects than positive control atromide. Therein, com Read More

Anticoagulants are used to prevent the formation and extension of blood clots in various disorders as prophylactic agents for thrombo-embolic disorders. Designing of specific inhibitors against molecular targets that play a pivotal role in the coagulation cascade is indispensable. Clotting Factor Xa is one such attractive target for the design of new oral anticoagulants because of the unique role factor Xa plays in the coagul Read More