Synthesis and in vitro Antimycobacterial Activity of Moxifloxacin Methylene and Ethylene Isatin Derivatives

A series of novel moxifloxacin methylene and ethylene isatin derivatives with remarkable improvement in lipophilicity, compared to the parent moxifloxacin, was designed, synthesized and characterized by 1H NMR, MS and HRMS. These derivatives were initially evaluated for their in vitro antimycobacterial activity against M. smegmatis CMCC 93202. Compounds 3a―3f, 5a, 5f and 5j were chosen for the further evaluation of their in vitro activity against Mycobacterium tuberculosis（MTB） H37Rv ATCC 27294 and MDR-MTB 09710. All the target com pounds[minimum inhibitory concentration（MIC）： 0.39―〉16 μg/mL] were far more active than rifampin（MIC： 2.0―〉256 μg/mL）, but less active than moxifloxacin（MIC： 0.1―1.0 μg/mL） against the three tested strains. The most active compounds 3a and 3c were found to be 2―64 fold more potent than isoniazid and rifampin against M. smegmatis CMCC 93202, 2 fold more potent than rifampin against MTB H37Rv ATCC 27294, and 16―〉64 fold more potent than ethambutol, isoniazid and rifampin against MDR-MTB 09710.

Evaluation of Antimycobacterial Activity of Higenamine Using Galleria mellonella as an In Vivo Infection Model

The Phytochemical investigation on MeOH extract on the bark of Aristolochia brasiliensis Mart.&Zucc(Aristolochi-aceae)led to the isolation of major compound(1)as light brown grainy crystals.The compound was identified as 1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol(higenamine)on the basis of spectroscopic analysis,including 1D and 2D NMR spectroscopy.The compound was evaluated for its antimycobacterial activity against Mycobacterium indicus pranii(MIP),using Galleria mellonella larva as an in vivo infection model.The survival of MIP infected larvae after a single dose treatment of 100 mg/kg body weight of higenamine was 80%after 24 h.Quantitatively the compound exhibited a dose dependent activity,as evidenced by the reduction of colony density from 10^(5) to 10^(3) CFU for test concentrations of 50,100,150 and 200 mg/kg body weight respectively.The IC50 value for higenamine was 161.6 mg/kg body weight as calculated from a calibration curve.Further analysis showed that,a complete inhibition of MIP in the G.mellonella could be achieved at 334 mg/kg body weight.Despite the fact that MIP has been found to be highly resistant against isoniazid(INH)in an in vitro assay model,in this study the microbe was highly susceptible to this standard anti-TB drug.The isolation of higenamine from the genus Aristolochia and the method used to evaluate its in vivo antimycobacterial activity in G.mellonella are herein reported for the first time.

Synthesis and antimycobacterial activity of ternatolide

Ternatolide isolated from Radix Ranuncoli Ternati is considered as the active ingredient against Mycobacterium tuberculosis. Herein, tematolide was synthesized in four steps in 32.7% overall yield by using Yamaguchi esterification as the key step, and its antimycobacterial activity was investigated in vitro using a rapid direct susceptibility assay. It was reported that ternatolide killed the Mycobacterium tuberculosis possibly by enhancing the expression of GLS in PBLs indirectly, and our results indicated that tematolide was weakly active against MTB H37Rv ATCC 27294 directly. Therefore, it can be concluded that its mechanism of action was possibly related to the cellular factors.

Anti-Mycobacterial Activity of Medicinal Plant Extracts Used in the Treatment of Tuberculosis by Traditional Medicine Practitioners in Uganda

Tuberculosis (TB) remains a public health challenge and one of the leading causes of death worldwide. TB is preventable and curable. However, treatment of tuberculosis has continued to be difficult as a result of rapid increase of multidrug and extensively drug resistant strains of Mycobacterium tuberculosis. Medicinal plants have for centuries been traditionally used in treatment of tuberculosis and similar ailments. They possess antimicrobial properties which render them a new hope as a source of novel bioactive leads in the development of antimycobacterial agents. In this study, 2 plant species commonly used traditionally in Uganda for treatment of tuberculosis, Zanthoxylum leprieurii and Rubia cordifolia were screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis strains;pan sensitive MTB H37Rv, Rifampicin resistant TMC 331 strain and two wild strains (one rifampicin resistant and another one rifampicin susceptible). Antimycobacterial activity of aqueous, ethanolic and methanolic plant extracts was determined using Resazurin Microtiter Assay (REMA). Both plant extracts exhibited significant in vitro antimycobacterial activity against all strains of Mycobacterium tuberculosis. Minimum inhibitory concentrations (MIC) of methanolic crude extracts of both plants ranged from 23.4 μg/mL to 187.5 μg/mL. Comparatively, methanol extracts of both plants possessed superior antimycobacterial activity against all Mycobacterium tuberculosis strains. Our findings indicated that both plants exhibited activity against susceptible and resistant strains of Mycobacterium tuberculosis. While antimycobacterial activity of Z. leprieurii confirms results from previous studies, activity of the extracts of R. cordifolia is reported for the first time in East Africa. Further studies aimed at determining the effects of combination of these plant extracts and standard anti-TB drugs should be carried out.

A Systematic Review on Antituberculosis Drug Discovery and Antimycobacterial Potential of Biologically Synthesized Silver Nanoparticles:Overview and Future Perspectives

Rapid emergence and quick evolution of drug-resistant and aggressive mycobacterial strains have resulted in the present antimycobacterial drug crisis and the persistence of tuberculosis as a major public health problem.Green/biological nanotechnologies constitute an interesting area of research for discovering antimycobacterial agents.This review focused on the biological(green)synthesis of silver nanoparticles(AgNPs)as an alternative source of antimycobacterial agents.Data for this study were searched and screened from three electronic databases(Google Scholar,PubMed and ScienceDirect)following the Preferred Reporting Items for Systematic Reviews and Meta-analyses flowchart.Data from in total 17 eligible studieswere reported in this systematic review.Twelve of the 17 studies used plants to fabricate AgNPs,whereas the remaining five studies used microorganisms(bacteria and/or fungi).Silver as part of silver nitrate(AgNO3)was themetal precursor reported for the synthesis of AgNPs in these studies.Silver nanoparticles were mostly spherical,with sizes ranging from12 to140nm.Resultsbasedon minimum inhibitory concentrations varied between studies and were divided into three groups:(i)those more effective than the antibiotic(controls),(ii)those more effective than plant extracts,and(iii)those less effective than the antibiotic controls.In addition,little or no cytotoxicity effects were reported.Silver nanoparticles were also shown to be highly specific or selective toward mycobacterial strains.This systematic review highlights the antimycobacterial potential of biologically synthesized AgNPs,underscoring the possibility of discovering/developing new antimycobacterial agents using biological synthesis approaches with less toxicity and high selectivity.

Bioactivity of selected seaweeds from gulf of Mannar,South-east cost of India

Objective:To evaluate antimicrobial and antimycobacterial activity of three seaweeds[Gelidiella acerosa(G.acerosa),Turbinaria conoides(T.conoides)and Sargassum wightii(S.wightii)]from Gulf of Manner.Methods:Three seaweeds G.acerosa,T.conoides and S.wightii were collected from Gulf of Mannar,South-East Coast of India.Solvent extraction of the selected seaweeds was done using hexane and ethanol.These extracts were tested for antibacterial activity against four bacterial strains(Escherichia coli,Pseudomonas aeruginosa,Bacillus subtilis and Staphylococcus aureus)by disc diffusion method.The active extracts of T.conoides were tested for antimycobacterial activity by luciferase reporter phage assay at two different concentrations(100μg/mL and 500μg/mL).Results:Among the tested seaweeds,ethanol extract of T.conoides showed maximum antibacterial activity against Bacillus subtilis and Staphylococcus aureus followed by hexane extract at concentration of 1 mg/disc.The remaining two seaweeds(G.acerosa and S.wightii)did not show any activity.The ethanol extract of T.conoides exhibited maximum antimycobacterial activity(87.33%)followed by hexane extract(74.68%)against Mycobacterium tuberculosis H37Rv at 500μg/mL.Conclusions:Ethanol extract of T.conoids showed both antibacterial and antimycobacterial activity.Further photochemical studies are needed to identify the active antimycobacterial agents.