Anti-Infective Agents - Volume 17, Issue 1, 2019

Background: Microbial infection and its resistance to clinically approved drugs create a huge threat to human health. Emerging reports have indicated the potential of statin drugs in the treatment of various types of microbial infections. However, it is still unclear, how much concentration of statin is effective against microbial infections. In literature, Minimum Inhibitory Concentration (MIC) values of statin drugs vary according to strain, species, and the type of statins. Thus, the main aim of the current study is to compare the MIC values of various types of statins against various types of micro-organisms. Methodology: The data related to statin and microbial infection has been extracted from Pub Med (from September 1987 to October 2017). A total of 662 studies have been published from 1987 -2017 regarding statin and microbial infections. After inclusion and exclusion criteria, finally, 28 studies have been selected for comparative analysis of MIC values. Results: All the statin drugs have shown a significant effect on various types of microbial infections. Among all the tested statin drugs, Simvastatin has lower MIC value in almost all types of microorganisms as compared to other statin drugs. However, on S. pneumoniae and aspergillus, Fluvastatin has the lowest MIC values as compared to Simvastatin. Atorvastatin was found to be the most potent against almost all strains of gram-negative bacteria. However, Rosuvastatin and Pravastatin have high MIC value against all types of microorganisms. Further, FICI value indicated the synergetic effect of Simvastatin with Amphotericin B, Itraconazole, and Fluconazole against various strains of Cryptococcus. Conclusion: In conclusion, Simvastatin, Atorvastatin, and Fluvastatin could be developed as potential antimicrobial agents. However, further studies are required to understand its complete safety and efficacy profile.

Introduction: Tuberculosis is an infectious bacterial disease that mainly affects the lungs. Globally, there are about 10.5 million new cases and about 1.5 million deaths reported each year as per science daily research news in 2017. Objective: One of the biggest problems of Tuberculosis is the lack of effective treatments. Bedaquiline (2013) and Delaminid (2014) are the only two agents approved for TB after Rifampicin. This clearly shows the need for new lead molecules to fight against TB. Methodology: A series of benzimidazolium and benzotriazolium derivatives were synthesized and the structures were confirmed by their IR, 1H NMR,13C NMR and mass spectral data. They were tested for in vitro antitubercular activity by MABA Assay, MTT Assay and axenic culture assay. To determine selective TB activity, they were also tested for antimicrobial activity and cytotoxicity. Docking simulations and drug-inhibitor combination studies were conducted to know the probable mechanism of action. Results: Among the synthesized compounds B10, B11, B13, B14, B22, B23, B24, B25, B26 and B27 showed excellent anti TB activity with an MIC 3.12-0.8 μg/mL. Among these, compound 1,3- bis(4-chlorobenzyl)-1H-benzo[d]imidazol-3-ium chloride (B11) has shown selective anti TB activity against Mycobacterium tuberculosis H37Rv (0.8μg/mL) in MABA assay. This compound hasn't shown any antimicrobial (at 100μg/mL) and cytotoxicity (at 10μM). Docking studies and drug-inhibitor combination studies indicated that the compounds might act via enzymes involved in the cell division process. Conclusion: In conclusion, we synthesized molecules with potent and selective anti TB activity.

Background: Antibiotics play an important role in the treatment of infections to the humans and at the same time, irrational, frequent prescription of higher antibiotics, change in gene composition of microorganisms are all the reasons behind the development and introduction of new antibiotics against different microorganisms. Objective: In this project, an attempt has been made to synthesize some derivatives of diazenyl containing phenyl styryl ketones and also their in vitro screening was conducted against Mycobacterium tuberculosis, Escherichia coli, Klebsiella pneumonia, Bacillus subtilis, Staphylococcus aureus, Aspergillus niger and Candida albicans. Methods: Ten molecules were synthesized which are diazenyl containing chalcones. 4- aminoacetophenone was diazotised and piperidine was coupled with the formed diazonium chloride. Further, the acetoxy group underwent Claisen-Schmidt condensation with differently substituted aldehydes to form the final compounds- the chalcones. The proposed chemical structures were confirmed by different spectroscopic techniques like FTIR, 1H NMR and Mass spectroscopy. TLC was used to know that the reactants were exhausted and the formation of the product occurred. Sharp melting point of the compounds concludes the purity. Results: The MIC of the compounds 3CP, 3DP, 3EP and 3GP is 20 times the MIC of the standard fluconazole drug against Aspergillus niger. The compound 3GP is as equipotent as the standard drug Pyrazinamide with MIC of 3.12 μg/ml against Mycobacterium tuberculosis. Conclusion: The results are quite promising which on further studies may lead to drug molecules against different microorganisms. Especially, 3EP can be considered as a broad spectrum agent due to its potent activity against different microorganisms like Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Candida albicans.

Background: The actinomycetes strains isolated from unexplored ecosystems are a promising alternative for the biosynthesis of novel antimicrobial compounds. Depending on the interesting antifungal activity of the studied strain S19, the statistical method seems to be an effective tool for optimizing the production of anticandidal molecules. Introduction: This study was conducted in order to optimize the culture parameters (medium nutrients concentrations and initial pH value) affecting the production of antifungal metabolites from S. albidoflavus strain S19 (obtained from wastewater collected in Bejaia region, Algeria) using Response Surface Methodology (RSM). The best conditions for anti-Candida albicans compounds biosynthesis were determined. Methods and Results: The antimicrobial producer strain S. albidoflavus S19 was identified on the basis of morphological, chemicals characters and physiological characteristics along with 16S rRNA gene sequencing analysis. Response Surface Methodology by Central Composite Design (CCD) was employed to improve the anti- C. albicans agents production through the optimization of medium parameters. The highest antifungal activity was obtained by using a mixture of 2g l-1 starch, 4g l-1 yeast extract, 2g l-1 peptone at pH 11. Conclusion: The strain S19 isolated from wastewater showed a significant anti-C. albicans activity and this study revealed the effectiveness of RSM and CCD for increasing bioactive compounds production, rising the diameter of inhibition zones from 13 to 34 mm.

Background: Neuroleptic phenothiazines have been reported for antitubercular activity, but the unwanted side effect (antipsychotic activity) restricted their use as antitubercular drugs. Objective: The study aimed to carry out development of phenothiazine based antitubercular agents by modifying/removing the chemical group(s)/ linker(s) of chlorpromazine essential for exerting an antipsychotic effect. Methods: The designed molecules were filtered with a cut-off of docking score < 2.0 Kcal/mol against dopamine receptors, so that their binding with the receptor would be reduced to produce no/ less antipsychotic effect. The molecules were then synthesized and screened against M. tuberculosis H37Rv. They were further screened against a gram-positive (S. aureus) and a gram-negative (E. coli) bacterial strains to evaluate the spectrum of activity. The ability of the compounds to cross the blood-brain barrier (BBB) was also analyzed. The compounds were further examined for cytotoxicity (CC50) against mammalian VERO cells. Results: Compounds 14p, 15p and 16p were found to be the most effective against all the strains viz. M. tuberculosis H37Rv, S. aureus and E. coli with MIC of 1.56μg/ml, 0.98μg/ml and 3.91μg/ml, respectively. Further, BBB permeability was found to be diminished in comparison to chlorpromazine, which would ultimately reduce the unwanted antipsychotic activity. They were also found to be free from toxicity against VERO cells. Conclusion: The designed strategy, to enhance the antitubercular activity with concomitant reduction of dopamine receptor binding and BBB permeability was proved to be fruitful.

Background: Nitrogen-containing heterocyclics are abundant in natural products and also in synthetic drug molecules because of a variety of applications and superior pharmacological profile action. Pyrazoles are the integral architects of many of the heterocyclic compounds with superior biological activity. Methods: Two series of the pyrazole conjugated Benzothiazole derivatives were synthesized. The pyrazoles were synthesized by the Vilsmeier-Haack reaction and then conjugated with benzothiazole hydrazine and hydrazide by imine bond formation. The synthesized compounds were screened for anti-mitotic activity using Allium assay. Results: Here, the anti-mitotic activity, the percentage of cell division and the percentage of inhibition compared to the control were calculated. Compound 4b (-OMe), 4c (-OH), 5b (-OMe), 5c (- OH) and 5d (-CH3) had electron donating groups which showed excellent activity, was followed by 4f and 5f where they contain p-Bromo substitution, showing moderate activity. Conclusion: In the two series, benzothiazole linked to pyrazole through the hydrazide bridging (5a-5i) had superior to hydrazine bridging (4a-4i). The observed chromosomal aberrations are because of the structural morphology and binding sites of the molecule with the chromosome.

Background: Seven compounds were isolated from Dracaena cochinchinensis and elucidated their structure by NMR spectroscopic analysis and determined the optical rotation for certain compounds. Methods: These compounds were screened for antibacterial activity by using agar well diffusion and determination of minimum inhibitory concentration (MIC) was conducted by the broth micro-dilution method using resazurin colorimetric assay. Further investigation on combination effect between each compound with chloramphenicol was conducted by agar well diffusion method. Among the seven compounds, compound 4 displayed the highest antibacterial activity against P. acnes and S. aureus with the inhibition zone of 17.3 and 16.7 mm, respectively. The MIC value of 1 and 4 against all tested bacteria was 62.5 μM, whereas those of other compounds were 62.5-250 μM. The combination of 4 and chloramphenicol exhibited the most synergistic effect against P. acnes with the rate in increasing antibacterial activity of 4 in combination as 1,250 folds. This compound also enhanced the antibacterial activity of chloramphenicol at 50 μM with an inhibition zone of 16.3 mm comparing to its activity alone (8.7 mm). Results & Conclusion: The results revealed compound 4 displayed the highest antibacterial activity alone and in combination with chloramphenicol against P. acnes and S. aureus.