Combination of the Topliss Approach with the Free-Wilson Analysis in the Study of Antimycobacterial Activityof 4-Alkylthiobenzanilides

1997 ◽  
Vol 62 (9) ◽  
pp. 1503-1510 ◽  
Author(s):  
Jiří Kuneš ◽  
Jiří Jáchym ◽  
Petr Jirásko ◽  
Želmíra Odlerová ◽  
Karel Waisser
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Avium ◽  
Steric Effect ◽  
Antimycobacterial Activity ◽  
Mycobacterium Fortuitum ◽  
Mycobacterium Kansasii ◽  
Isopropyl Group ◽  
Butyl Group ◽  
Preliminary Study ◽  
Cyclohexyl Group

On the basis of a preliminary study of the antimycobacterial activity of thiobenzanilides, a group of 4'-isopropyl- and 4'-butylthiobenzanilides have been synthesized and tested against Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium and Mycobacterium fortuitum. The effect of the substituents on minimum inhibitory concentrations was calculated by the Free-Wilson method. The separated values were analyzed by the Topliss approach. The substitution of the thiobenzanilide in position 4' by the isopropyl group or butyl group increased the antimycobacterial activity less than the cyclohexyl group. The substitution in position 4 decreased the activity by the steric effect.

Antituberculotic 4'-Cyclohexylthiobenzanilides: Combination of Free-Wilson Method in QSAR with Topliss Approach

1993 ◽  
Vol 58 (1) ◽  
pp. 205-212 ◽  
Author(s):  
Karel Waisser ◽  
Lenka Kubicová ◽  
Želmíra Odlerová
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimycobacterial Activity ◽  
Significant Activity ◽  
Mycobacterium Kansasii ◽  
Type Analysis ◽  
Qsar Analysis ◽  
Preliminary Study

On the basis of a preliminary study of antimycobacterial activity of thiobenzanilides against Mycobacterium kansasii, a group of 4'-cyclohexylthiobenzanilids have been prepared which exhibit a significant activity against the microorganism mentioned. The whole set of 35 thiobenzanilides was tested with Mycobacterium tuberculosis, and on the basis of QSAR analysis conclusions have been made with regard to prognostics of structures suitable for further studies. The problem was solved by the method by Free and Wilson combined with the Topliss approach and by a Hansch type analysis.

On the Relationship between the Structure and Antimycobacterial Activity of Substituted N-Benzylsalicylamides

2003 ◽  
Vol 68 (7) ◽  
pp. 1275-1294 ◽  
Author(s):  
Karel Waisser ◽  
Milan Peřina ◽  
Věra Klimešová ◽  
Jarmila Kaustová
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Avium ◽  
Antimycobacterial Activity ◽  
Acyl Moiety ◽  
Mycobacterium Kansasii ◽  
Hammett Constants ◽  
Substituent Constants ◽  
The Relationship ◽  
Lipophilicity Parameters

Sixty-six N-benzylsalicylamides substituted in the acyl moiety in positions 3, 4 or 5 and in position 4 on the benzylic aromatic ring were synthesized. The compounds were tested for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium. To evaluate structure-antimycobacterial activity relationships (QSARs), approaches based on the Free-Wilson as well as a combination of the Free-Wilson and Hansch methods were employed (substituent constants were used to describe the influence of the benzyl substituents, indicator parameters were used for the substituents on the acyl moiety). The use of the Hammett constants for benzyl substituents was not important for QSAR equations. The quadratic representation of lipophilicity parameters (π2) was significant only in QSAR equations of antimycobacterial activity against M. avium.

scholarly journals Assessment of Morphology for Rapid Presumptive Identification of Mycobacterium tuberculosis andMycobacterium kansasii

2000 ◽  
Vol 38 (4) ◽  
pp. 1426-1429 ◽  
Author(s):  
Silvia Attorri ◽  
Sherry Dunbar ◽  
Jill E. Clarridge
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Avium ◽  
Cost Effective ◽  
Mycobacterium Kansasii ◽  
Specific Training ◽  
Predictive Values ◽  
Morphologic Characteristics ◽  
Cost Effective Method ◽  
Probe Selection ◽  
Presumptive Identification

Mycobacterium tuberculosis often exhibits serpentine cording when grown in liquid medium, whereas Mycobacterium kansasii can be larger and cross-barred. We assessed the use of these morphologic characteristics as a cost-effective method for rapid presumptive identification of isolates from BACTEC bottles. Without specific training, using the Kinyoun acid-fast stain, definitive cording was found in 237 of 373 specimens positive forM. tuberculosis (64%) and cross-barring was recognized within 63 of 76 (83%) of the specimens positive for M. kansasii, giving sensitivities specificities, positive predictive values, and negative predictive values of 63.5, 96, 92, and 79%, respectively, for M. tuberculosis and 83, 95, 59, and 98%, respectively, for M. kansasii. With training and experience, these results improved to 74.5, 98, 96, and 84% and 93, 98, 79, and 98%, respectively. The major improvements were in distinguishing the pseudocording, or loose aggregation ofMycobacterium avium complex from M. tuberculosis and the long beaded forms of Mycobacterium gordonae from M. kansasii. Mycobacterium asiaticum and Mycobacterium szulgai, which rarely occur, are genetically related to M. kansasiiand morphologically difficult to distinguish. In defined circumstances, serpentine cording and cross-barring can be used for rapid presumptive identification of M. tuberculosisand M. kansasii, respectively, and as guides for initial probe selection to reduce costs.

scholarly journals Induction of autophagy by trehalose limits opportunistic mycobacterial infections in HIV-infected macrophages

2017 ◽  
Author(s):  
Vartika Sharma ◽  
Muzamil Makhdoomi ◽  
Purnima Kumar ◽  
Nabab Khan ◽  
Sarman Singh ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Avium ◽  
Defense Mechanisms ◽  
Bacterial Infections ◽  
Opportunistic Infections ◽  
Mycobacterium Fortuitum ◽  
Mycobacterial Infections ◽  
Innate Defense ◽  
Treatment Naïve ◽  
Immense Potential

AbstractOpportunistic bacterial infections amongst HIV-infected individuals pose serious health challenge. While immediate control of bacterial pathogens is typically attributed to innate defense mechanisms, whether HIV-mediated modulation of innate mechanisms like autophagy promote opportunistic infections, remains obscure. Using U1.1 and U937 macrophages, we show, HIV activation or infection inhibits autophagy and helps survival of pathogenic Mycobacterium tuberculosis and non-pathogenic non-tuberculous mycobacterial strains (NTMs) like Mycobacterium avium complex and Mycobacterium fortuitum. HIV achieves this by blocking xenophagy flux, which could be reversed by the autophagy inducer trehalose that kills intracellular Mtb and NTMs. We found trehalose acts as a PI (3,5) P2 agonist and activates TRPML1 to induce autophagy. Remarkably, trehalose treatment significantly reduced p24 levels in PBMCs infected with clinical HIV strains and in PBMCs derived from treatment-naive HIV patients. Taken together, our study highlights the immense potential of autophagy modulators in the therapeutic intervention of HIV and associated opportunistic infection.

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