Crystal structure of the apurinic/apyrimidinic endonuclease XthA (HP1526 protein) from Helicobacter pylori.

Helicobacter pylori is a bacterium that causes gastritis, peptic ulcer disease and adenocarcinoma while infecting human stomach. In the stomach H. pylori is under stresses caused by reactive oxygen and nitrogen species from host immune response, which causes oxidative DNA damage.

Design, synthesis, and evaluation of novel -substituted-1-(4-chlorobenzyl)-1-indol-3-carbohydrazides as antitumor agents.

In continuity of our search for novel anticancer agents acting as procaspase activators, we have designed and synthesised two series of ()-'benzylidene-carbohydrazides () and -(2-oxoindolin-3-ylidene)carbohydrazides () incorporating 1-(4-chlorobenzyl)-1-indole core. Bioevaluation showed that the compounds, especially compounds in series , exhibited potent cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). Within series , compounds with 2-OH substituent () exhibited very strong cytotoxicity in three human cancer cell lines assayed with IC values in the range of 0.

Novel 3,4-dihydro-4-oxoquinazoline-based acetohydrazides: Design, synthesis and evaluation of antitumor cytotoxicity and caspase activation activity.

In search for novel small molecules with antitumor cytotoxicity via activating procaspase-3, we have designed and synthesized three series of novel (E)-N'-benzylidene-4-oxoquinazolin-3(4H)-yl)acetohydrazides (5a-j, 6a-h, and 7a-h). On the phenyl ring ò the benzylidene part, three different substituents, including 2-OH-4-OCH, 4-OCH, and 4-N(CH), were introduced, respectively. Biological evaluation showed that the acetohydrazides in series 5a-j, in which the phenyl ring of the benzylidene part was substituted by 2-OH-4-OCH substituent, exhibited potent cytotoxicity against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung).

Crystal structure of an iron superoxide dismutase from the pathogenic amoeba Acanthamoeba castellanii.

The iron superoxide dismutase found in the pathogenic amoeba Acanthamoeba castellanii (AcFeSOD) may play essential roles in the survival of the parasite, not only by protecting it from endogenous oxidative stress but also by detoxifying oxidative killing of the parasite by host immune effector cells. The AcFeSOD protein was expressed in a stable form using an Escherichia coli expression system and was crystallized by the microbatch and hanging-drop vapour-diffusion methods. The structure was determined to 2.

Novel 3-substituted-2-oxoindoline-based N-hydroxypropenamides as histone deacetylase inhibitors and antitumor agents.

Histone deacetylases (HDAC) are currently a group of validated targets for anticancer drug discovery and development. In our research program to find novel small molecules targeting these enzymes, we designed and synthesized two series of 3-hydroxyimino-2-oxoindoline- and 3- methoxyimino-2-oxoindoline-based N-hydroxypropenamides (3a-g, 6a-g). The results show that these propenamides potently inhibited HDAC2 with IC50 values in sub-micromolar range, approximately 10-fold lower than that of SAHA (also known as suberoylanilohydroxamic acid).

5-aryl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents: synthesis, bioevaluation and docking study.

The search for newer histone deacetylase (HDAC) inhibitors has attracted a great deal of interest of medicinal chemists worldwide, especially after the first HDAC inhibitor (Zolinza(®), widely known as SAHA or Suberoylanilide hydroxamic acid) was approved by the FDA for the treatment of Tcell lymphoma in 2006. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-aryl-1,3,4-thiadiazole-based hydroxamic acids as analogues of SAHA and evaluated their biological activities. Most of the compounds in this series, e.

Novel isatin-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents.

Accumulated clinical studies have demonstrated that histone deacetylase (HDAC) inhibitors show great potential for the treatment of cancer. SAHA (Vorinostat, trade name Zolinza) was approved by the FDA in 2006 for the treatment of the cutaneous manifestations of cutaneous T-cell lymphoma. As a continuity of our ongoing effort to identify novel small molecules targeting these important enzymes, we designed and synthesized two series of isatin-3'-oxime- and isatin-3'-methoxime-based hydroxamic acids (3a-g and 6a-g) as analogues of SAHA.

Synthesis, bioevaluation and docking study of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents.

Since the first histone deacetylase (HDAC) inhibitor (Zolinza®, widely known as suberoylanilide hydroxamic acid; SAHA) was approved by the Food and Drug Administration for the treatment of T-cell lymphoma in 2006, the search for newer HDAC inhibitors has attracted a great deal of interest of medicinal chemists worldwide. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as analogues of SAHA and evaluated their biological activities. A number of compounds in this series, for example, N(1)-hydroxy-N(8)-(5-(2-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (5b), N(1)-hydroxy-N(8)-(5-(3-chlorophenyl-1,3,4-thiadiazol-2-yl)octandiamide (5c) and N(1)-hydroxy-N(8)-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (5d), were found to possess potent anticancer cytotoxicity and HDAC inhibition effects.

New benzothiazole/thiazole-containing hydroxamic acids as potent histone deacetylase inhibitors and antitumor agents.

Results from clinical studies have demonstrated that inhibitors of histone deacetylase (HDAC) enzymes possess promise for the treatment of several types of cancer. Zolinza(®) (widely known as SAHA) has been approved by the FDA for the treatment of T-cell lymphoma. As a continuity of our ongoing research to find novel small molecules to target these important enzymes, we synthesized a series of benzothiazole-containing analogues of SAHA and found several compounds with very potent anticancer cytotoxicity.

Benzothiazole-containing hydroxamic acids as histone deacetylase inhibitors and antitumor agents.

Data from clinical studies indicate that inhibitors of Class I and Class II histone deacetylase (HDAC) enzymes show great promise for the treatment of cancer. Zolinza (SAHA, Zolinza) was recently approved by the FDA for the treatment of the cutaneous manifestations of cutaneous T-cell lymphoma. As a part of our ongoing effort to identify novel small molecules to target these important enzymes, we have prepared two series of benzothiazole-containing analogues of SAHA.

Mass screening of prostate cancer in Vietnam: current status and our opinions.

Background: Although prostate cancer (CaP) is the most common male cancer in developed countries, the incidence of CaP in Vietnam remains unknown and the patients often seek treatment at a late stage in their illness. The mass screening of CaP, which has been performed since Jan 2008 in Binh Dan hospital (Ho Chi Minh City) aims to evaluate the effect of CaP mass screening in Vietnam. The details of CaP treatment from 1999 to now in Ho Chi Minh City (HCMC) were also used for evaluation and comparison.