New Groups of Potential Antituberculotics: Bis(1-aryltetrazol-5-yl) Disulfides. Structure Activity Relationship

1994 ◽  
Vol 59 (1) ◽  
pp. 234-238 ◽  
Author(s):  
Karel Waisser ◽  
Jiří Kuneš ◽  
Alexandr Hrabálek ◽  
Želmíra Odlerová
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Antimycobacterial Activity ◽  
Activity Relationship ◽  
Active Derivative ◽  
Structure Activity ◽  
Medium Activity ◽  
Substituent Constants ◽  
Atypical Strains

Oxidation of 1-aryltetrazole-5-thiols afforded bis(1-aryltetrazol-5-yl) disulfides. The compounds were tested for antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, M. avium and M. fortuitum. In the case of M. tuberculosis, the logarithm of minimum inhibitory concentration showed a parabolic dependence on hydrophobic substituent constants. Although the compounds exhibited low to medium activity, the most active derivative, bis(4-chlorophenyltetrazol-5-yl) disulfide (III) was more effective against atypical strains than are the commercial tuberculostatics used as standards.

scholarly journals Synthesis and anti-tubercular activity of 3-substituted benzothiophene-1,1-dioxides

2014 ◽  
Author(s):  
N. Susantha Chandrasekera ◽  
Mai A Bailey ◽  
Megan Files ◽  
Torey Alling ◽  
Stephanie K Florio ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Minimum Inhibitory Concentration ◽  
Mode Of Action ◽  
Drug Targets ◽  
Inhibitory Concentration ◽  
Eukaryotic Cells ◽  
Structure Activity ◽  
Novel Drug ◽  
Further Development ◽  
Novel Drug Targets

We demonstrated that the 3-substituted benzothiophene-1,1-dioxide class of compounds are effective inhibitors of Mycobacterium tuberculosis growth under aerobic conditions. We examined substitution at the C-3 position of the benzothiophene-1,1-dioxide series systematically to delineate structure-activity relationships influencing potency and cytotoxicity. Compounds were tested for inhibitory activity against virulent M. tuberculosis and eukaryotic cells. The tetrazole substituent was most potent, with a minimum inhibitory concentration (MIC) of 2.6 µM. However, cytotoxicity was noted with even more potency (Vero cell TC50 = 0.1 µM). Oxadiazoles had good anti-tubercular activity (MICs of 3–8 µM), but imidazoles, thiadiazoles and thiazoles had little activity. Cytotoxicity did not track with anti-tubercular activity, suggesting different targets or mode of action between bacterial and eukaryotic cells. However, we were unable to derive analogs without cytotoxicity; all compounds synthesized were cytotoxic (TC50 of 0.1–5 µM). We conclude that cytotoxicity is a liability in this series precluding it from further development. However, the series has potent anti-tubercular activity and future efforts towards identifying the mode of action could result in the identification of novel drug targets.

scholarly journals Synthesis and anti-tubercular activity of 3-substituted benzothiophene-1,1-dioxides

2014 ◽  
Author(s):  
N. Susantha Chandrasekera ◽  
Mai A Bailey ◽  
Megan Files ◽  
Torey Alling ◽  
Stephanie K Florio ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Minimum Inhibitory Concentration ◽  
Mode Of Action ◽  
Drug Targets ◽  
Inhibitory Concentration ◽  
Eukaryotic Cells ◽  
Structure Activity ◽  
Novel Drug ◽  
Further Development ◽  
Novel Drug Targets

We demonstrated that the 3-substituted benzothiophene-1,1-dioxide class of compounds are effective inhibitors of Mycobacterium tuberculosis growth under aerobic conditions. We examined substitution at the C-3 position of the benzothiophene-1,1-dioxide series systematically to delineate structure-activity relationships influencing potency and cytotoxicity. Compounds were tested for inhibitory activity against virulent M. tuberculosis and eukaryotic cells. The tetrazole substituent was most potent, with a minimum inhibitory concentration (MIC) of 2.6 µM. However, cytotoxicity was noted with even more potency (Vero cell TC50 = 0.1 µM). Oxadiazoles had good anti-tubercular activity (MICs of 3–8 µM), but imidazoles, thiadiazoles and thiazoles had little activity. Cytotoxicity did not track with anti-tubercular activity, suggesting different targets or mode of action between bacterial and eukaryotic cells. However, we were unable to derive analogs without cytotoxicity; all compounds synthesized were cytotoxic (TC50 of 0.1–5 µM). We conclude that cytotoxicity is a liability in this series precluding it from further development. However, the series has potent anti-tubercular activity and future efforts towards identifying the mode of action could result in the identification of novel drug targets.

Synthesis of carbohydrate-substituted isoxazoles and evaluation of their antitubercular activity

2017 ◽  
Vol 23 (3) ◽  
pp. 225-229 ◽  
Author(s):  
Khaoula Hajlaoui ◽  
Ahlem Guesmi ◽  
Naoufel Ben Hamadi ◽  
Moncef Msaddek
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Minimum Inhibitory Concentration ◽  
Bacterial Strain ◽  
Inhibitory Concentration ◽  
Cycloaddition Reaction ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Dipolar Cycloaddition ◽  
Nitrile Oxides ◽  
Mycobacterium Tuberculosis H37rv

AbstractEight new sugar-substituted isoxazoles were synthesized by a 1,3-dipolar cycloaddition reaction of aromatic nitrile oxides with carbohydrate-substituted alkynes. Products were screened for antimycobacterial activity against the Mycobacterium tuberculosis H37Rv strain. Four compounds, 5e–h, significantly inhibit growth of the bacterial strain with a minimum inhibitory concentration (MIC) of 3.125 μg/mL.

scholarly journals The Chemical Composition and Anti-mycobacterial Activities of Trachyspermum copticum and Pelargonium graveolens Essential Oils

2020 ◽  
Vol 15 (1) ◽  
pp. 68-74 ◽  
Author(s):  
Jalil Kardan-Yamchi ◽  
Mohaddese Mahboubi ◽  
Hossein Kazemian ◽  
Gholamreza Hamzelou ◽  
Mohammad M. Feizabadi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Chemical Composition ◽  
Minimum Inhibitory Concentration ◽  
Essential Oil ◽  
Essential Oils ◽  
Inhibitory Concentration ◽  
Mycobacterium Fortuitum ◽  
Drug Resistant ◽  
Pelargonium Graveolens ◽  
Trachyspermum Copticum

Background: Microbial resistance to antibiotics and their adverse effects related to these antibiotics are a matter of global public health in the 21th century. The emergence of drug-resistant strains, has gained the interest of the scientists to discover new antimicrobial agents from the essential oil of medicinal plants. Methods: Anti-mycobacterial effects of Trachyspermum copticum and Pelargonium graveolens essential oils were determined against multi-drug resistant clinical strains of Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium fortuitum and standard strain of Mycobacterium tuberculosis H37Rv by a Broth micro-dilution method. Pelargonium graveolens plant named Narmada was discovered by Kulkarni R.N et al. (Patent ID, USPP12425P2) and a formulation comprising thymol obtained from Trachyspermum is useful in the treatment of drug-resistant bacterial infections (Patent ID, US6824795B2). The chemical composition of hydro-distilled essential oils was determined by GC and GC-MS. Results: Minimum Inhibitory Concentration (MIC) values for T. copticum essential oil against tested isolates were ranged from 19.5 µg/mL to 78 µg/mL. The least minimum inhibitory concentration of P. graveolens extract against M. Kansasii and MDR-TB was 78 µg/ml. Conclusion: The results of the present research introduced T. copticum and P. graveolens essential oils as a remarkable natural anti-mycobacterial agent, but more pharmacological studies are required to evaluate their efficacy in animal models.

scholarly journals Investigation of 5’-Norcarbocyclic Nucleoside Analogues as Antiprotozoal and Antibacterial Agents

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3433 ◽  
Author(s):  
Anastasia Khandazhinskaya ◽  
Elena Matyugina ◽  
Pavel Solyev ◽  
Maggie Wilkinson ◽  
Karen Buckheit ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Biological Activity ◽  
Antibacterial Agents ◽  
Structure Activity Relationship ◽  
Nucleoside Analogues ◽  
Activity Relationship ◽  
Carbocyclic Nucleosides ◽  
Structure Activity ◽  
Small Structure ◽  
Relationship Study

Carbocyclic nucleosides have long played a role in antiviral, antiparasitic, and antibacterial therapies. Recent results from our laboratories from two structurally related scaffolds have shown promising activity against both Mycobacterium tuberculosis and several parasitic strains. As a result, a small structure activity relationship study was designed to further probe their activity and potential. Their synthesis and the results of the subsequent biological activity are reported herein.

Synthesis and structure–activity relationships of novel abietane diterpenoids with activity against Staphylococcus aureus

2019 ◽  
Vol 11 (24) ◽  
pp. 3109-3124
Author(s):  
Macarena Funes Chabán ◽  
Antonia I Antoniou ◽  
Catherine Karagianni ◽  
Dimitra Toumpa ◽  
Mariana Belén Joray ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Minimum Inhibitory Concentration ◽  
Toxic Effect ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Dehydroabietic Acid ◽  
Target Cells ◽  
Structure Activity ◽  
Abietane Diterpenoids ◽  
Relationship Study

Aim: To find alternative compounds against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA), novel derivatives from dehydroabietic acid were synthesized. Methods & results: Compound 12 was the most effective against 15 MRSA and 11 MSSA with minimum inhibitory concentration values ranging from 3.9 to 15.6 μg/ml. Although less active than 12, compound 11, followed by 25 and 13, also exhibited anti-staphylococcal activity. Additional studies showed that compound 12 is devoid of toxic effect on non-target cells. A structure–activity relationship study revealed that an oxime at C-13 together with a hydroxyl at C-12 could play a key role in the activity. Conclusion: These structures, in particular compound 12, could arise as templates for the development of agents against MRSA and MSSA.

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