Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 15, Issue 2, 2015

Hydrazones are a versatile linker of connecting various classes of organic compounds with a unique structural feature of hydrogen bonding donor and the hydrogen bonding acceptor region. An extensive number of research has been carried out on hydrazone derivatives as a potent class of antitubercular agents. The present review focuses on the chemistry, antitubercular activity and structure activity relationship (SAR) of diverse classes of phenyl and heterocyclic based hydrazones.

Dental caries is a widely prevalent infectious disease afflicting the humans worldwide. Each year oral infections such as dental caries, periodontal diseases and oral candidiasis significantly adds to the economic burden of the world. Though there are standard management techniques for these diseases; they do have side effects and are not cost effective. Ayurveda is a traditional Indian system of medicine that is being practiced in the Indian peninsula since ages. Among the various herbal medicines in ayurveda, triphala occupies a royal position due to its wide beneficial systemic actions. Triphala is a mixture of fruits of Terminalia bellirica, Terminalia chebula and Emblica officinalis. The antimicrobial actions of triphala are well documented in the literature. However availability of review articles regarding triphala as an antimicrobial against oral infections is limited. Need was felt to review this aspect of triphala. The present article reviews the use of triphala and its constituents in the prevention and control of dental caries and other common oral infections. Thorough review of the literature indicated that triphala can be effectively used to manage dental caries, gingival and periodontal diseases. Further it can also be utilized as a root canal irrigant and against oral candida species.

Backgrounds: Beta thalassemia is a hereditary blood disorder characterized by reduced or absent beta chains of hemoglobin resulting in imbalanced globin chain synthesis with early destruction of RBCs and anemia. Patients with thalassemia major become transfusion- dependent with subsequent iron overload. Effective iron chelation therapy remains the main target of management of thalassemia major. Objectives: ‘The aim of this work was to compare the efficacy of different iron chelating agents in the treatment of iron overload in children with beta thalassemia major. Patients and Methods: ‘The current study was conducted on 120 children with beta thalassemia major with serum ferritin level of more than 1000 ng/ml who were divided into 4 groups’: Group A: 30 patients were treated with 8 hours intravenous infusion of Desferrioxamine, 40 mg/kg/day, 6 days per week for 6 months. Group B: 30 patients were treated with subcutaneous infusion of Desferrioxamine, 40 mg/kg/day, 6 days per week 8-12 hours per day at night using Desferal pump for 6 months. Group C: 30 patients were treated with oral Deferiprone 75 mg/kg/day in three divided doses daily for 6 months. Group D: 30 patients were treated with oral Deferasirox 30 mg/kg/day in single dose on empty stomach daily for 6 months. For all patients laboratory investigations were carried out including complete blood count (CBC), measurement of serum ferritin, serum iron, TIBC (total iron binding capacity), liver enzymes and kidney functions. Results: There were significant reductions in serum ferritin and serum iron after treatment in all studied groups with the highest reduction in group A, group B, group D and group C but without statistically significant differences between the four studied groups before and after chelation therapy. ‘There were no significant differences in the mean values of the parameters of CBC, liver enzymes and kidney functions between the studied groups before and after chelation therapy. Conclusion: From this study we concluded that there was significant reduction in serum ferritin and serum iron after chelation therapy in studied groups with the highest reduction in group A (IV Desferrioxamine), group B (SC Desferrioxamine), group D (oral Deferasirox) and group C (oral Deferiprone) with no statistically significant differences between the studied groups of patients before and after 6 months of regular chelation.

Helicobacter pylori colonizes the stomach, causing gastritis, peptic ulcers and gastric carcinoma. Drugs for treatment of H. pylori relieve from gastritis or pain but are not specific to H. pylori. Therefore, there is an immediate requirement for new therapeutic molecules to treat H. pylori. Current study investigates identification of drug targets in the strain HPAG1 of H. pylori by in silico genome analysis. Genome of HPAG1 was reconstructed for metabolic pathways and compared with Homosapien sapiens to identify genes which are unique to H. pylori. These unique genes were subjected to gene property analysis to identify the potentiality of the drug targets. Among the total number of genes analysed in H. pylori strain HPAG1, nearly 542 genes qualified as unique molecules and among them 29 were identified to be potential drug targets. Co/Zn/Cd efflux system membrane fusion protein, Ferric sidephore transport system and biopolymer transport protein EXbB were found to be critical drug targets to H. pylori HPAG1. Five genes (superoxide dismutase, HtrA protease/chaperone protein, Heatinducible transcription repressor HrcA, HspR, transcriptional repressor of DnaK operon, Cobalt-zinccadmium resistance protein CzcA) of the 29 predicted drug targets are already experimentally validated either genetically or biochemically lending credence to our unique approach.

Background: The purpose of the present study was the distribution of blaOXA-1, blaPER-1 and blaVEB genes and the genotyping of these genes in extended-spectrum β-lactamases (ESBL) producing uropathogenic and diarrheagenic Escherichia coli isolates. Methods: Of 432 isolates, 58 uropathogenic E. coli (UPEC) and 56 diarrheagenic E. coli (DEC) isolates were shown to produce the ESBLs. The isolates were screened to present ESBLs genes by PCR. Pulsed-Field Gel Electrophoresis (PFGE) was used to genotype E. coli strains which possess ESBLs genes. Results: The blaOXA-1 gene was detected in 17.24% of UPEC isolates and 1.78% of DEC isolates. Of all the isolates studied, none were positive for the blaPER-1 and blaVEB genes. PFGE revealed that the E. coli isolates possessed blaOXA-1 gene comprised three distinct genotypes. Conclusions: The current study illustrated high rates of ESBL-resistant phenotypes of E. coli isolates from urine and diarrhea samples in Iran. The blaOXA-1, blaPER-1 and blaVEB genes were found at low frequencies in studied isolates.

Trichomoniasis is a sexually transmitted disease (STD) caused by a tiny parasite called Trichomonas vaginalis. Metronidazole is used as routine treatment of disease. Some reports have confirmed the potential carcinogenic and teratogenic effects of this drug on fetus and indication of drug resistance. Verbascum thapsus belongs to the family of Scorphulariaceae. Its antiinflammatory properties, disinfectant and skin healing effects are well known. This plant has been used to treat diarrhea and genitourinary infection in traditional medicine. Effects of different concentrations of the Verbascum thapsus extract were tested on the growth and motility of T.vaginalis trophozoites. To evaluate the toxicity of extract, their effects on mice macrophages were measured by MTT([3-(4,5-dimethyl thiazolyl-2)- 2,5-diphenyle tetrazolium bromide ])assay. In this experimental study the effect of Verbascum Thapsus ethanol extract on induction apoptosis in T. vaginalis was determined by Flow Cytometry. Results were analyzed by Flow Jo software and the degree of apoptosis was determined. Toxicity percentage of 25-800 μg/ml concentrations of Verbascum thapsus alcoholic extract for mice macrophages was observed between 0.17-0.25 after 12 hours and they were between 0.25-0.42 and0.45-0.95 after 24 and 48h respectively. IC50 (inhibitory concentration, 50%) of Verbascum thapsus ethanol extract and metronidazole after 24h was 39.17 and 0.0326 μg/ml respectively. Flow cytometry results showed the percent of apoptosis following treatment of trophozoites with different concentrations of Verbascum thapsus ethanol extract (25, 50,100,200,400 μg/ml), were 20.7, 37.04, 47.5, 62.72 and 86.35 respectively, while in control group was 2.9. According to this study, Verbascum thapsus extract induces programmed death in T. vaginalis. It is recommended that Verbascum thapsus extract can be considered as a suitable choice for Medical Studies.

Background: Piperine is isolated from Piper nigrum popularly known as black pepper. Previous studies have demonstrated the beneficial effects of piperine in various health conditions. Additionally, it is a powerful bioenhancer for many drugs. Piperine extract is believed to potentiate the effect of drugs by several folds. The present study is focused on its individual effect on liver function. Materials and methods: A total of 30 CF-1 albino mice obtained from the animal house of faculty of Medicine, Benghazi University, Benghazi, Libya were included in the study. These mice were fed with high cholesterol diet and divided into 2 groups. Twenty mice were administered piperine at a dose of 5mg/kg body weight. Piperine was isolated in Department of Pharmacognosy, Faculty of Pharmacy, Benghazi University, Benghazi and 10 mice were not administered piperine but fed with high fat diet. These mice were anesthetized with ketamine and halothane and blood was drawn from each mouse before the study and after three weeks by cardiocentesis. Serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), alkaline phosphatase and total protein were measured by authenticated methods. Results: Serum alanine amino transferase was significantly elevated (p=0.0002) in group A mice after the administration of Piperine extract for three weeks compared to those of group B mice. Serum aspartate amino transferase was elevated significantly (p=0.046) and alkaline phosphatase (p= 0.0001) also was significantly increased after the administration of piperine. Serum total protein (p= 0.011) values were significantly decreased after the use of piperine for three weeks in group A mice. Conclusion: This study showed that there might have been a considerable damage to liver with piperine extract. Further research may be required to prove this damage to liver function.

Almost any species of non tuberculosis mycobacterium [NTM], including M. chelonae may be associated with nosocomial infections including catheter related sepsis, pneumonia etc. We present a case of catheter related sepsis due to M. chelonae which was treated with appropriate therapy including removal of the catheter. This case serves as a reminder to include the NTM group in the differential diagnosis of these nosocomial infections.