Constituents of Fagraea fragrans with Antimycobacterial Activity in Combination with Erythromycin

Background: Mycobacterium tuberculosis is a causative organism of tuberculosis, which is most deadly disease after cancer in a current decade. The development of multidrug and broadly drug- resistant strains making the tuberculosis problem more and more critical. In last 40 years, only one molecule is added to the treatment regimen. Generally, drug design and development programs are targeted proteins whose function is known to be essential to the bacterial cell. Objectives: Reported here are the development of 'S', 'N’ heterocycles as antimycobacterials targeting fatty acid biosynthesis. Material and Methods: In the present communication, rational development of anti-mycobacterial agent's targeting fatty acid biosynthesis has been done by integrating the pocket modelling and virtual analysis. Results: The identified potential 33 lead compounds were synthesized, characterized by physicochemical and spectroscopic methods like IR, NMR spectroscopy and further screened for antimycobacterial activity using isoniazid as standard. All the designed compounds have shown profound antimycobacterial activity. Conclusion: In this present communication, we found that 3c, 3f, 3l and 4k molecules had expressive desirable biological activity and specific interactions with fatty acids. Further optimization of these leads is necessary for the development of potential antimycobacterial drug candidate having less side effects.

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

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19940234 ◽

1994 ◽

Vol 59 (1) ◽

pp. 234-238 ◽

Cited By ~ 7

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.

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Relations between Structure and Antituberculotic Activity of 4-Alkoxybenzoic Acids

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19930191 ◽

1993 ◽

Vol 58 (1) ◽

pp. 191-196 ◽

Cited By ~ 6

Author(s):

Karel Waisser ◽

Jiří Kuneš ◽

Jiří Klimeš ◽

Miroslav Polášek ◽

Želmíra Odlerová

Keyword(s):

Active Compound ◽

Antimycobacterial Activity ◽

Methoxybenzoic Acid

Antimycobacterial activity of a series of alkoxybenzoic acids including 4-methoxybenzoic acid (II), 4-ethoxybenzoic acid (III), 4-propoxybenzoic acid (IV), 4-butoxybenzoic acid (V), 4-pentoxybenzoic acid (VI), 4-allyloxybenzoic acid (IX), 4-isopropoxybenzoic acid (VII), 4-isobutoxybenzoic acid (VIII) and 4-benzyloxybenzoic acid (X) has been determined and found to increase with the lipophilicity of the compounds expressed by the corresponding HPLC capacity factors. Also determined were the pKa values of the compounds mentioned. The most active compound, 4-pentoxybenzoic acid (VI), is comparable with commercial antituberculotics when tested in vitro.

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ChCl: Gly (DESs) Promote Environmentally Benign Synthesis of Xanthene Derivatives and Their Antitubercular Activity

Molecules ◽

10.3390/molecules26123667 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3667

Author(s):

Mashooq A. Bhat ◽

Ahmed M. Naglah ◽

Siddique Akber Ansari ◽

Hanaa M. Al-Tuwajiria ◽

Abdullah Al-Dhfyan

Keyword(s):

Reaction Times ◽

Antitubercular Activity ◽

Antimycobacterial Activity ◽

Environmentally Benign ◽

Reaction Yield ◽

Benign Synthesis ◽

Xanthene Derivatives ◽

Wide Range ◽

Major Application

A ChCl: Gly (DESs) promoted environmentally benign method was developed for the first time using the reaction of aryl aldehydes and dimedone to give excellent yields of xanthene analogues. The major application of this present protocol is the use of green solvent, a wide range of substrate, short reaction times, ease of recovery, the recyclability of the catalyst, high reaction yield, and ChCl: Gly as an alternative catalyst and solvent. In addition to this, all the synthesized compounds were evaluated for their in vitro antimycobacterial activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. The compounds 3d, 3e, 3f, and 3j showed significant antitubercular activity against MTB and M. bovis strains with minimum inhibitory concentration (MIC) values of 2.5−15.10 µg/mL and 0.26–14.92 µg/mL, respectively. The compounds 3e, 3f, and 3j were found to be nontoxic against MCF-7, A549, HCT 116, and THP-1 cell lines. All the prepared compounds were confirmed by 1H NMR and 13C NMR analysis.

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Atypically Modified Carbapenem Antibiotics Display Improved Antimycobacterial Activity in the Absence of β-Lactamase Inhibitors

ACS Infectious Diseases ◽

10.1021/acsinfecdis.1c00185 ◽

2021 ◽

Author(s):

Rashmi Gupta ◽

Noora M. S. A. Al-Kharji ◽

Maha A. Alqurafi ◽

Thu Q. Nguyen ◽

Weirui Chai ◽

...

Keyword(s):

Antimycobacterial Activity

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Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis

Nature Communications ◽

10.1038/s41467-021-21748-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Poushali Chakraborty ◽

Sapna Bajeli ◽

Deepak Kaushal ◽

Bishan Dass Radotra ◽

Ashwani Kumar

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune System ◽

Biofilm Formation ◽

Antimycobacterial Activity ◽

Drug Tolerance ◽

Host Immune System ◽

Tissue Sections ◽

Slow Growing

AbstractTuberculosis is a chronic disease that displays several features commonly associated with biofilm-associated infections: immune system evasion, antibiotic treatment failures, and recurrence of infection. However, although Mycobacterium tuberculosis (Mtb) can form cellulose-containing biofilms in vitro, it remains unclear whether biofilms are formed during infection in vivo. Here, we demonstrate the formation of Mtb biofilms in animal models of infection and in patients, and that biofilm formation can contribute to drug tolerance. First, we show that cellulose is also a structural component of the extracellular matrix of in vitro biofilms of fast and slow-growing nontuberculous mycobacteria. Then, we use cellulose as a biomarker to detect Mtb biofilms in the lungs of experimentally infected mice and non-human primates, as well as in lung tissue sections obtained from patients with tuberculosis. Mtb strains defective in biofilm formation are attenuated for survival in mice, suggesting that biofilms protect bacilli from the host immune system. Furthermore, the administration of nebulized cellulase enhances the antimycobacterial activity of isoniazid and rifampicin in infected mice, supporting a role for biofilms in phenotypic drug tolerance. Our findings thus indicate that Mtb biofilms are relevant to human tuberculosis.

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Isonicotinoyl hydrazones of pyridoxine derivatives: synthesis and antimycobacterial activity

Medicinal Chemistry Research ◽

10.1007/s00044-021-02705-w ◽

2021 ◽

Author(s):

Nikita V. Shtyrlin ◽

Rail M. Khaziev ◽

Valery G. Shtyrlin ◽

Edward M. Gilyazetdinov ◽

Mariya N. Agafonova ◽

...

Keyword(s):

Antimycobacterial Activity

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