Anti-Infective Agents - Volume 16, Issue 1, 2018

The WHO has estimated that one-fourth of the world's population harbor a latent infection by MTB, and around 100-200 million individuals eventually develop an active TB. To make matters worse, drug-resistant MTB as well as the co-infection between MTB and HIV has further aggravated the mortality and spread of this disease. The quinolones have contributed an increasingly important chapter to the evolution of antimicrobials, and some of them were recommended as the second-line agents for the treatment of TB by WHO. Numerous 2-quinolone-based derivatives have been synthesized for searching new anti-TB agents, and some of them showed promising potency. This review aims to outline the recent advances made towards the discovery of 2-quinolone-based derivatives as potential anti-TB agents, and their structure-activity relationships are also discussed.

Background: The problem of bacterial resistance of Mycobacterium tuberculosis should be solved by seeking for alternative substances that potentially inhibit the growth or kill the bacteria. Ganoderma lucidum is one type of fungus which is potential to be an antimicrobial agent. This study aimed to determine the potential of G. lucidum on inhibiting the growth of multidrug-resistant bacteria of M. tuberculosis in vitro. Methods: This study used a solid dilution method to test the extract of G. lucidum as an antibacterial agent. Results and Conclusion: Results showed that all strains of multidrug-resistant tuberculosis (MDR-Tb) gave similar responses to G. lucidum extract at various concentrations. The bacteria did not grow on the medium containing G. lucidum extract at the smallest concentration of 12.5%, as well as concentrations of 25% and 50%. Ganoderma lucidum can be used as one of the alternatives for MDR-Tb drugs in the future.

Objectives: Pharmacokinetics of dapaconazole and inhibition of cytochrome P450 family 51. Methods: Pharmacokinetics of dapaconazole, a novel imidazolic antifungal compound, was studied in male beagle dogs following intravenous (1, 2 and 20 mg/kg) and oral (20 mg/kg) administration. Results: Oral bioavailability was calculated to be 97.3%. The elimination half-life (t½) after intravenous administration was 2.1-2.5 h, the total body clearance was 2.5-4.2 L/h/kg and the apparent volume of distribution was 9.0-14.4 L/kg. Dapaconazole caused concentration-dependent inhibition of cytochrome P450 family 51 (CYP51) activity with an IC50 of 1.4 ± 0.3 μM (mean ± SEM, n=3), compared to that of ketoconazole (IC50 = 1.2 ± 0.6 μM, n=3). Conclusion: Results indicate that dapaconazole could be a potentially useful drug for systemic administration.

Background: According to global eradication initiative program, poliomyelitis was eradicated all over the world except Pakistan and Afghanistan due to some challenges like misconceptions, non-compliances, political and militancy issues, etc. Objective: This study quantitatively evaluates the knowledge, attitude and perception of general public regarding polio and its vaccination in district Abbottabad and Mansehra, KPK, Pakistan. Method: A cross sectional study design involving 800 participants was conducted from November 2015 to February 2016 in district Abbottabad and Mansehra of KPK, Pakistan. To collect the data from eligible participants, pre tested self-administered questionnaire was used. Descriptive and binary logistic regression analysis was used to express the results of the study. Results: A total of 53.8% participants exhibited appropriate knowledge about polio and its vaccination. Higher qualification (p<0.001), urban locality (p<0.05), paid employed (p<0.05) and primary information source (p<0.001) were significantly associated with appropriate knowledge of polio and its vaccination. About 71.6% of the participants showed positive attitude towards polio and its vaccination. Older age (p<0.001), self-employment (p<0.05), high income (p<0.001), urban residence (p<0.001) and primary information source i.e. village and community leaders (p<0.05) were significantly associated with the positive attitudes of participants towards polio and its vaccination. About 56.90% participants had wrong perception about which treatment is best for polio. Overall perception about polio and its vaccination was significantly associated with participants of older age (p<0.001), gender specially females (p<0.05), employment status i.e. self- employment (p<0.001), higher income (p<0.001), marital status (p<0.05) and urban residency (p<0.05). Conclusion: This study identified some important issues related to polio vaccination which can help in eradicating polio by effective immunization campaigns in Pakistan.

Background: The increasing predominance of microbial resistance towards available antimicrobial drugs urges the need to develop novel antimicrobial agents that will be effective against resistant bacteria and fungi. Objective: A series of 3-(benzothiazol-2-yl)-2-(4-substituted phenyl) thiazolidin-4-one derivatives were synthesized as pharmacophore hybrid of benzothiazole and thiazolidin-4-one moieties as exclusive antimicrobial agents. Methods: Proposed compounds were synthesized by four step reactions. First three steps involved synthesis of phenylthiourea, benzothiazol-2-ylamine and Schiff's base srespectively. Finally, Schiff`s baseswere cyclized in the presence of thioglycolic acid to yield 4-thiazolidinone derivatives (2a-g), characterized by spectroscopic and elemental analysis. Resulted compounds were evaluated for their in vitro antimicrobial activities against four bacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) and two fungal (A. niger and P. crysogenum) strains using agar diffusion method. The minimum inhibitory concentrations (MIC) of the synthesized compounds were also determined by tube dilution method. Results: All the compounds displayed good to moderate antimicrobial activity. Compound 2d was found most potent against Bacillus subtilis (MIC25μg/ml), whereas compound 2e was most active (MIC 25μg/ml) against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Conclusion: The compounds having electron-withdrawing groups in the phenyl ring exhibited promising activity. A correlation between the antimicrobial activity and Log P was also established. Most active compounds can be considered as the potential antibacterial agents and deserve further investigation for their pharmacological and toxicological profiling.

Background: Today infectious microbial diseases are causing complications world-wide, since resistance to a number of antimicrobial agents (β-lactam antibiotics, macrolides, quinolones, and vancomycin). A range of clinically important species of microorganisms has become a significant health problem globally. Methods: In quest of new antimicrobial agents with enhanced potency, a series of 6-aryl-3-[(2,3,4- substituted) phenyl]-[1,2,4]triazolo [3,4-b][1,3,4] thiadiazole (5a-5l) were synthesized by condensing 4- amino-5-[(2,3,4-substituted) phenyl]-4H-[1,2,4]- triazole-3-thiol (4) with various aromatic carboxylic acids in the presence of phosphorous oxychloride through one-pot reaction. The structures of these newly synthesized compounds were elucidated by elemental analysis, IR, 1H NMR and mass spectral data. All the synthesized compounds were screened for their in vitro antibacterial and antifungal activities against pathogenic microorganisms using two fold serial dilution method. Results: Several compounds showed favorable antimicrobial activity among which, compound 5e exhibited highest activity while compounds 5h and 5d presented promising antimicrobial activity against all the tested microorganisms comparable to reference drugs gentamicin and miconazole. However, when compared to fluconazole, the test compound 5e had lesser estimated binding free energy and predicted inhibitory constant values. Conclusion: From the current study it may be concluded that synthesized compounds are fulfilling in terms of their structural distinctiveness and marked biological properties. The molecular docking studies have amplified the scope of evolving a new class of antimicrobial agents.

Background: Chemotherapy of schistosomiasis by certain drugs is impractical due to the resistance of Schistosoma larvae to schistosomiasis drugs after long treatment period. The aim of this work is to monitor Schistosoma mansoni infection on mice livers after treatment with the ethanolic extract of Justicia spicigera areal parts and the herbal antishistosomal drug (Mirazid); the oleo-resin extract from Myrrh of Commiphora molmol tree. Methods: Liver function enzymes; Aspartate Aminotransferase (AST); Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Gamma Glutamyl Trans- Peptidase (GGT) and serum total protein content were estimated. Oxidative stress markers; Malondialdehyde (MDA), Glutathione (GSH) and Super Oxide Dismutase (SOD) were also evaluated. Parasitological and histopathological studies through numbers of worm burden and liver pathology pattern were done. Results: The results showed obvious decreases in AST, ALT, ALP, GGT, total protein, MDA and SOD after treatment with plant extract or the selected drug, while GSH recorded significant increase after treatment. A noticeable decrease in worm count and an improvement in histopathological picture of the infected mice liver were detected. Conclusion: The ethanolic extract of Justicia spicigera areal parts recorded antioxidants and antischistosomal effects. Further work is needed to validate its safety and for considering it as anti-schisotosomal drug.

Introduction: In the last two-three decades, antimicrobial infections have developed extreme multiple drug-resistance and the appearance of these resistant strains is one of the biggest threats to global health. The benzothiazole moiety is of interest to many researchers on the grounds that they constitute a vital class of heterocyclic compounds exhibiting enormous chemotherapeutic activities. In the drug design aspect, structure activity relationship (SAR) study is an area of exploring and continuously refining the structural or physical properties for evoking the promising biological effects. Methods: The present study discusses the synthesis of new antimicrobial candidates using the pharmacophore hybrids of benzothiazole and thiophene scaffold. In an attempt to identify potential lead antimicrobial agents, a number of N-(substituted-benzothiazol-2-yl)thiophene-2-carboxamidederivatives were efficiently synthesized by conventional synthesis and screened in order to evaluate for their antibacterial activity against Staphylococcus aureus (ATCC-25923) and Escherichia coli (ATCC-25922) and antifungal activity against Aspergillus niger (ATCC- 9029) and Candida albicans (ATCC-90028) in DMF by serial plate dilution method. Results: Amongst the synthesized compounds, compound 3g showed significant antibacterial activity and antifungal activity. Rest of the compounds showed moderate to less antibacterial activity against both S. aureus and E. Coli. and antifungal activity against A. niger and C. albicans. The SAR studies demonstrate that introducing an electron-withdrawing group at the aromatic ring has favorable effect on the antimicrobial activity. A correlation study was also used to establish the relationship between the activity and physicochemical parameter clogP. Titled compounds could be a promising template for future antimicrobial drug development. Discussion: The synthesized compounds were characterized by elemental and spectral data analysis. Antimicrobial activity of the title compounds has been evaluated by varying the substituents in the benzothiazol moiety.

Introduction: A series of seventeen 1-phenyl-3-(5-phenyl-1H-imidazol-1-yl) thiourea derivatives (5a-8d) were synthesized and characterized by physical and spectral data (IR, 1H NMR, and mass spectroscopy) and evaluated for their antibacterial and antifungal activities against various pathogenic and non-pathogenic microorganisms. Some of the synthesized compounds showed promising antibacterial and antifungal activities. Results and Discussions: Many of the tested compounds were found to be significantly active against gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and gram-negative bacterial strains (Escherichia coli, Salmonella typhi, Klebsiella pneumoniae and Pseudomonas aeruginosa), among which compounds 5a, 5b, 6a, 6b, 7a, 7b, 8a and 8b showed the maximum anti-bacterial activity but less effective than the standard ciprofloxacin. Almost all compounds from 5a-8d showed moderate activity against fungal strains like Candida albicans and Aspergillus niger.