Anti-Infective Agents - Volume 13, Issue 2, 2015

Introduction: H. pylori is a flagellate Gram-negative bacterium living on the mucosal surface of the gastric epithelium. It is accepted that the antibiotic resistance is a major problem for treatment of diseases caused by infectious bacteria. Infection is generally acquired during childhood and persists life-long in the absence of antibiotic treatment. Because of development of quinolone-resistant pathogens, quinolone-based triple therapy is not recommended as first-line therapy. In the case of H. pylori treatment we should also be well prepared to face with H. pylori treatment failures. Methods: To determine current status of the treatment failure, we have investigated recent papers in databases. Results: After the failure of first and second lines therapy of H. pylori infection, a culture-guided therapy has been recommended. Local surveillance of antibiotic resistance for all antibiotics used in H. pylori eradication regimens seems a practically possible suggestion to battle against this mysterious infection. More research is required to develop more effective therapeutic approaches. Conclusion: The main aims should be the maintenance of a high eradication rate of H. pylori and also successful prevention actions of increased antibiotic resistance. The purpose of this review is to provide an overview about the current knowledge of H. pylori treatment in 2015; also suggesting possible solutions for difficulties in close future.

Background: The recent emergence of multi-drug resistant (MDR) and extensively drugresistant (XDR) cases of tuberculosis has lead to the search for new structural classes of anti-TB drugs that can be effective against these strains of Mycobacterium tuberculosis. In the present study a series of 2-thiazolylimino-5-arylidene-4-thiazolidinone derivatives, unsubstituted and mono-substituted with hydroxy, methoxy, fluoro, chloro and nitro groups on the aryl ring were synthesized and assayed for their in vitro antimycobacterial activity against drug-sensitive M. tb H37Rv strain. Methods: In vitro antimycobacterial activity against drug-sensitive M. tb H37Rv strain (susceptible both to rifampicin and isoniazid) was performed and expressed as % inhibition at minimum inhibitory concentration (MIC) values. Compounds were initially tested for IC99 at a concentration of 6.25 μg/ml in BACTEC-460 TB radiometric system, and Isoniazid (0.1 μg/ml) and rifampicin (2.0 μg/ml) were taken as reference standards. Results: We report the synthesis and antimycobacterial activities of 2- thiazolylimino-5-arylidene-4-thiazolidinone derivatives, expressed as % inhibitions, and their MIC values. All of the above synthesized compounds showed substantial antimycobacterial activity in the preliminary screening, and some of the compounds, 8-14, exhibited excellent antimycobacterial activities (86-98 % inhibition) at 6.25–12.5 μg/ml against drugsensitive M. tb H37Rv strain. Conclusion: The 2-thiazolylimino-5-arylidene-4-thiazolidinone derivatives were identified as a new antitubercular chemical entity in this study. Two of the active compounds, 9 and 14 and their derivatives have been identified as potential lead molecules for further drug development. It was observed that the hydroxyl and bulky alkoxy groups enhance antimycobacterial activity, while a halogen substituent decreases the activity. Further structural optimization and identification of molecules are underway in our laboratory..

Background: Tuberculosis is responsible for the world’s leading cause of death affecting one third of the world’s population by the latent or dormant form despite the current chemotherapy. For the effective management of MDR or XDR-TB, new lead compounds or novel therapeutic targets are urgently needed. The present investigation is aimed at creating a new and hitherto unreported molecular framework encompassing isoxazole moiety with carboxamide derivatives for the antitubercular activity. Methods: 5-methylisoxazole-3-carboxamide derivatives (4-20) were synthesized in good yield and were characterised by, spectral studies. In vitro antitubercular activity of the synthesized compounds was determined against Mycobacterium tuberculosis H37Rv by MABA method and in vitro antibacterial activity against Bacillus subtilis and Escherichia coli by serial dilution method. Results: The titled compounds, 10 and 14 showed significant antitubercular activity with MIC of 3.125 μM and 9 and 13 with MIC of 6.25 μM among the tested compounds. The active compounds have shown good safety profile against Vero and HepG2 Cell lines. The compounds 9, 13, 19 and 20 showed significant antibacterial activity with MIC of 6.25 μM and 15 and 17 showed activity with MIC of 12.5 μM among the tested compounds. Conclusion: In conclusion, we reported the convenient synthetic method for the 5-methylisoxazole-3-carboxamides. The results of antitubercular activity were encouraging. With structure base drug design approach and suitable molecular modifications of the synthesized compounds 9, 10, 13 and 14, it is possible to develop lead molecule with better antitubercular potential.

Background/Purpose: Medicinal plant extracts with potent antimicrobial activity are potentially useful sources of new and novel antimicrobial agents. We investigated the extracts from the stem bark of Macaranga rosea antimicrobial activity. Methods: Cold extraction procedures were used to obtain extracts followed by standard qualitative assays for phytochemicals. Agar well diffusion and macrobroth dilution assays were used to determine antimicrobial effects of the extracts. Thin layer and column chromatography were used to further separate the chemical entities for further clues on the active constituents. Results: The Methanolic extracts provided the greatest diversity of phytochemicals including reducing sugars, anthraquinones, Phlobatannins, glycosides, steroids, tannins, saponins and alkaloids. Ethanol extracts were the most effective against Staphylococcus aureus and Pseudomonas aeruginosa whilst methanolic extracts were more effective against Candida albicans. The MIC and MBC values were lowest with the methanolic extracts for S. aureus with values of 3.12 and 6.25 mg/ml for MIC and MBC respectively. For P. aeruginosa, the ethanolic extract gave the best MIC and MBC values of 1.56 and 3.12 mg/ml respectively. For C. albicans, the best MIC and MFC values were obtained from methanolic extracts at 0.78 and 3.12 mg/ml respectively. Fractions of the methanolic extracts were active against Pseudomonas aeruginosa and Candida albicans but not S. aureus at 250μg/ml. Conclusion: This study demonstrated the phytochemical richness and wide spectrum of antimicrobial activity of Macaranga rosea. The plant is currently endangered and this study appears to be the first documented on its antimicrobial properties.

Background: Pyrazole, oxazole and pyrimidine are nitrogen containing heterocycles which possess very good binding efficiency with receptor or proteins. Due to this effect it can be work as antitubercular agents with active substituents. The objective of this paper is clubbed the heterocycles to enhance their antitubercular potency. Methods: The active substituted pyrazole aldehydes were synthesized by reaction of phenyl hydrazine with different acetophenone followed by Vilsmeier-Haack formylation reaction. The isoxazole and aminopyrimidines were prepared by condensation of various chalcones with hydroxyl amine hydrochloride and guanidine hydrochloride respectively. The structures of the newly synthesized compounds were characterized by 1H-NMR, Mass, IR and elemental analysis data. All the newly synthesized compounds were screened for their antibacterial activity against Gram-positive S.pyogenus and Gram negative E.coli, Paeruginosa, S.aureus and antitubercular activity against mycobacterium tuberculosis H37Rv. Results: Oxygen containing substituent in aromatic ring or heterocycles as a substituent were enhancing the antitubercular activity as compared to the other substituents. Ethoxy group present as a substituent in aromatic ring shows minimum inhibition concentration as compared to others. Conclusion: X-ray crystallographic study enhances that E-isomer formed in case of chalcones. The electron withdrawing group such as fluorine and chlorine enhancing the activity of Isoxazole and Pyridine as compare to the chalcones. Electron donating group such as ethoxy is increase the potency of the compounds at para position.

Background: A series of sixteen novel isatin analogs (3a-3p) have been synthesized and evaluated for their antibacterial and antifungal activities against various pathogenic microorganisms. Gram-positive bacterial strains: Staphylococcus aureus, Bacillus subtilis; Gram-negative bacterial strains: Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Klebsiella pneumonia, and fungal strains Candida albicans, Aspergillus niger use two fold serial dilution method. Methods: Some of the synthesized compounds showed promising antibacterial and antifungal activities among the series. Results: Compound 3l shows the best antimicrobial activity which is substantiated by the highest docking score. Conclusion: Structure activity relationships (SAR) as well as virtual ADMET studies were carried out and a connection between activities, electronic and physicochemical properties of the target compounds was determined.

Background: Dihydropyrimidinone is considered as a pharmacophoric skeleton in many drug discovery programmes. To explore the activity of dihydropyrimidines, we regioselectively synthesized some of the substituted mannich bases of dihydropyrimidinone (DHPM) analogues regioselectively with fluoroquinolones (Ciprofloxacin). Methods: Regioselectivity in these structures is achieved by the influence of weak base like potassium carbonate and synthesized some novel dihydropyrimidine N- and O-Mannich bases of ciprofloxacin (3a-j, 4a-g) using microwave technology. All the synthesized molecules have been evaluated for their antiviral activity against hepatitis C, hepatitis B, vaccinia, cowpox, severe acute respiratory syndrome, West Nile, dengue, Venezuelan equine encephalitis viruses, Flu A (H1N1, H3N2 and H5N1) and Flu B viral strains as well as for their cytotoxicity using standard protocols. Results: An attempt was made to interpret the structure activity relation of compounds with their antiviral activity data. Compounds 3a, 3e, 3f, 4e, 4g were found to be active against Flu A (H1N1), TCRV, hepatitis B, yellow fever, vaccinia virus respectively. Conclusion: Some of the synthesized compounds exhibited potent activity against some viral strains. Out of O- and N-mannich bases, O-mannich bases were found to be more potent with high selectivity index.