scholarly journals Nitrotriazole- and Imidazole-Based Amides and Sulfonamides as Antitubercular Agents

2014 ◽  
Vol 58 (11) ◽  
pp. 6828-6836 ◽  
Author(s):  
Maria V. Papadopoulou ◽  
William D. Bloomer ◽  
Howard S. Rosenzweig ◽  
Alexander Arena ◽  
Francisco Arrieta ◽  
...  
Keyword(s):  
Reduction Potential ◽  
Inhibitory Concentration ◽  
Antitubercular Agents ◽  
Low Oxygen ◽  
Cell Viability Assay ◽  
Content Type ◽  
Viability Assay ◽  
Resistant Strains ◽  
Electron Reduction ◽  
The One

ABSTRACTTwenty-three 3-nitrotriazole-based and 2-nitroimidazole-based amides and sulfonamides were screened for antitubercular (anti-TB) activity in aerobicMycobacterium tuberculosisH37Rv by using the BacTiter-Glo (BTG) microbial cell viability assay. In general, 3-nitrotriazole-based sulfonamides demonstrated anti-TB activity, whereas 3-nitrotriazole-based amides and 2-nitroimidazole-based amides and sulfonamides were inactive. Three 3-nitrotriazole-based sulfonamides (compounds 4, 2, and 7) demonstrated 50% inhibitory concentration (IC50), IC90, and MIC values of 0.38, 0.43, and 1.56 μM (compound 4), 0.57, 0.98, and 3.13 μM (compound 2), and 0.79, 0.87, and 3.13 μM (compound 7), respectively. For 3-nitrotriazole-based sulfonamides, anti-TB activity increased with lipophilicity, whereas the one-electron reduction potential (E1/2) did not play a role. 2-Nitroimidazole-based analogs, which were inactive in the BTG assay, were significantly more active in the low-oxygen assay and more active than the 3-nitrotriazoles. All active nitrotriazoles in the BTG assay were similarly active or more potent (lower MIC values) against resistant strains, with the exception of compounds 2, 3, 4, and 8, which demonstrated greater MIC values against isoniazid-resistant strains. Five 3-nitrotriazole-based sulfonamides demonstrated activity in infected murine J774 macrophages, causing log reductions similar to those seen with rifampin. However, some compounds caused toxicity in uninfected macrophages. In conclusion, the classes of 3-nitrotriazole-based amides and sulfonamides merit further investigation as potential antitubercular agents.

scholarly journals One-Electron Reduction Potentials: Calibration of Theoretical Protocols for Morita–Baylis–Hillman Nitroaromatic Compounds in Aprotic Media

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2129 ◽  
Author(s):  
Amauri Francisco da Silva ◽  
Antonio João da Silva Filho ◽  
Mário Vasconcellos ◽  
Otávio Luís de Santana
Keyword(s):  
Cyclic Voltammetry ◽  
Biological Activity ◽  
Chemical Structure ◽  
Reduction Potential ◽  
Chemical Reactivity ◽  
Nitroaromatic Compounds ◽  
Reduction Potentials ◽  
Electron Reduction ◽  
The One ◽  
Antileishmanial Activities

Nitroaromatic compounds—adducts of Morita–Baylis–Hillman (MBHA) reaction—have been applied in the treatment of malaria, leishmaniasis, and Chagas disease. The biological activity of these compounds is directly related to chemical reactivity in the environment, chemical structure of the compound, and reduction of the nitro group. Because of the last aspect, electrochemical methods are used to simulate the pharmacological activity of nitroaromatic compounds. In particular, previous studies have shown a correlation between the one-electron reduction potentials in aprotic medium (estimated by cyclic voltammetry) and antileishmanial activities (measured by the IC50) for a series of twelve MBHA. In the present work, two different computational protocols were calibrated to simulate the reduction potentials for this series of molecules with the aim of supporting the molecular modeling of new pharmacological compounds from the prediction of their reduction potentials. The results showed that it was possible to predict the experimental reduction potential for the calibration set with mean absolute errors of less than 25 mV (about 0.6 kcal·mol−1).

scholarly journals Use of the NP-40 Detergent-Mediated Assay in Discovery of Inhibitors of β-Hematin Crystallization

2011 ◽  
Vol 55 (7) ◽  
pp. 3363-3369 ◽  
Author(s):  
Rebecca D. Sandlin ◽  
Melissa D. Carter ◽  
Patricia J. Lee ◽  
Jennifer M. Auschwitz ◽  
Susan E. Leed ◽  
...  
Keyword(s):  
Drug Target ◽  
Inhibitory Concentration ◽  
Protozoan Parasite ◽  
Drug Resistant ◽  
Digestive Vacuole ◽  
Content Type ◽  
Parasite Survival ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Important Drug

ABSTRACTThe protozoan parasite responsible for malaria affects over 500 million people each year. Current antimalarials have experienced decreased efficacy due to the development of drug-resistant strains ofPlasmodiumspp., resulting in a critical need for the discovery of new antimalarials. Hemozoin, a crystalline by-product of heme detoxification that is necessary for parasite survival, serves as an important drug target. The quinoline antimalarials, including amodiaquine and chloroquine, act by inhibiting the formation of hemozoin. The formation of this crystal does not occur spontaneously, and recent evidence suggests crystallization occurs in the presence of neutral lipid particles located in the acidic digestive vacuole of the parasite. To mimic these conditions, the lipophilic detergent NP-40 has previously been shown to successfully mediate the formation of β-hematin, synthetic hemozoin. Here, an NP-40 detergent-based assay was successfully adapted for use as a high-throughput screen to identify inhibitors of β-hematin formation. The resulting assay exhibited a favorableZ′ of 0.82 and maximal drift of less than 4%. The assay was used in a pilot screen of 38,400 diverse compounds at a screening concentration of 19.3 μM, resulting in the identification of 161 previously unreported β-hematin inhibitors. Of these, 48 also exhibited ≥90% inhibition of parasitemia in aPlasmodium falciparumwhole-cell assay at a screening concentration of 23 μM. Eight of these compounds were identified to have nanomolar 50% inhibitory concentration values near that of chloroquine in this assay.

Electrochemical properties and catalytic reactivity of cobalt complexes with redox-active meso-substituted porphycene ligands

2020 ◽  
Vol 24 (01n03) ◽  
pp. 90-97 ◽  
Author(s):  
Taro Koide ◽  
Zihan Zhou ◽  
Ning Xu ◽  
Yoshio Yano ◽  
Toshikazu Ono ◽  
...  
Keyword(s):  
Reduction Potential ◽  
Energy Levels ◽  
Cobalt Complexes ◽  
Alkyl Halides ◽  
Reduction Potentials ◽  
Positive Side ◽  
Redox Active ◽  
Catalytic Reactivity ◽  
Electron Reduction ◽  
The One

The cobalt complexes of meso-aryl substituted porphycenes were synthesized and characterized. The reduction potentials of the complexes were shifted to the positive side depending on the strength of the electron-withdrawing properties of the meso-substituents, while the optical properties, such as the absorption spectra of these complexes, were similar. This suggests that the energy levels of the molecular orbitals of the complexes were changed by the meso-substituents while the gaps of the orbitals were not significantly changed. The one-electron reduction of the complex did not afford the Co(I) species, but the ligand-reduced radical anion, which was characterized by electrospectrochemistry. The generated ligand-reduced species reacted with alkyl halides to form the Co(III)-alkyl complex. As a result, the reduction potential of the electrolytic reaction could be directly controlled by the substituents of the porphycene. The catalytic reaction with trichloromethylbenzene was also performed and it was found that the ratio of the obtained products was changed by the reduction potentials of the catalyst, [Formula: see text]. the cobalt porphycenes.

ChemInform Abstract: The One-Electron Reduction Potential of 4-Substituted Phenoxyl Radicals in Water.

ChemInform ◽  
1990 ◽  
Vol 21 (17) ◽  
Author(s):  
J. LIND ◽  
X. SHEN ◽  
T. E. ERIKSEN ◽  
G. MERENYI
Keyword(s):  
Reduction Potential ◽  
Phenoxyl Radicals ◽  
Electron Reduction ◽  
The One

The One-Electron Reduction Potential of Methionine-Containing Peptides Depends on the Sequence

2012 ◽  
Vol 116 (31) ◽  
pp. 9352-9362 ◽  
Author(s):  
Jacqueline Bergès ◽  
Pedro de Oliveira ◽  
Isabelle Fourré ◽  
Chantal Houée-Levin
Keyword(s):  
Reduction Potential ◽  
Electron Reduction ◽  
The One

scholarly journals The m6A Methyltransferase METTL3 Promotes Cisplatin Resistance and Invasion in Testicular Seminoma via BCL2

2021 ◽  
Author(s):  
jingxuan peng ◽  
Yali Xiang ◽  
Wenfei Lian ◽  
Hanfei Chen ◽  
Dongyi Peng ◽  
...  
Keyword(s):  
Cell Invasion ◽  
Cisplatin Resistance ◽  
Invasion Assay ◽  
Cell Viability Assay ◽  
Testicular Seminoma ◽  
Treatment Target ◽  
Rna Methylation ◽  
Viability Assay ◽  
Resistant Strains ◽  
M6a Rna Methylation

Abstract Background: Methyltransferase-like 3 (METTL3) involves in promoting tumor progression through tumor-related genes N6-methyladenosine (m6A) modification. Our previous study found that METTL3 plays an important role in seminoma chemosensitivity. BCL-2 is a key cause of cisplatin resistance in many tumors. Therefore, we want to explore whether METTL3 affects cisplatin resistance of seminoma by regulating BCL-2.Methods: In this study, we downregulated and overexpressed METTL3 in TCam-2 cisplatin resistant cells (TCam-2/CDDP). Then, m6A RNA methylation quantification of BCL-2 and cell viability assay, cell apoptosis analysis and cell invasion assay were investigated under the condition of with or without cis‐dichlorodiammine platinum (CDDP) treatment. Results: Consistent with our previous results, METTL3 significantly affects the chemosensitivity of TCam-2/CDDP. After METTL3 downregulated, the proliferation and anti-apoptosis ability of TCam-2/CDDP cells significantly weakened. Correspondingly, overexpression of METTL3 could promote the chemoresistance. However, the phenotype could be partly reversed by decreasing the expression of BCL-2. Moreover, we found that the m6A modification of BCL-2 is more abundant in cisplatin-resistant strains. Knockdown and overexpression of METTL3 significantly affected the m6A modification and the protein level of BCL-2 in TCam-2/CDDP. Finally, we found that METTL3 also promoted the invasion ability of TCam-2/CDDP cells via BCL2.Conclusion: This study revealed that METTL3 promotes anti-apoptosis and invasion of TCam-2/CDDP through BCL-2. And it indicated that METTL3 and BCL-2 may be an effective treatment target for CDDP-resistance seminoma.

scholarly journals In Vitro Synergism of Rifabutin with Clarithromycin, Imipenem, and Tigecycline against the Mycobacterium abscessus Complex

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Aristine Cheng ◽  
Yi-Tzu Tsai ◽  
Shu-Yuan Chang ◽  
Hsin-Yun Sun ◽  
Un-In Wu ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Mycobacterium Abscessus ◽  
First Line ◽  
Content Type ◽  
Mycobacterium Abscessus Complex ◽  
Potential Synergy ◽  
Resistant Strains ◽  
Reference Strains

ABSTRACT Infections caused by the difficult-to-treat bacterium Mycobacterium abscessus are increasing in frequency. Rifabutin, in contrast to rifampin, appears to be active in vitro against M. abscessus, especially against clarithromycin-resistant strains. However, explorations for potential synergy between rifabutin and available antimicrobials are currently limited. In vitro synergism between rifabutin and 10 antimicrobials was evaluated in 31 mycobacterial strains by the checkerboard method. The fractional inhibitory concentration index (FICI) was calculated for each rifabutin-based combination. The colony morphology was recorded. Molecular methods for determination of the M. abscessus subspecies and analysis of macrolide resistance were performed by sequencing of the secA1, rpoB, hsp65, erm(41), and rrl genes. Rifabutin yielded an MIC50 of 16 mg/liter (range, 2 to 32 mg/liter) against 26 clinical M. abscessus isolates (comprising 13 M. abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates) and 5 reference strains, including M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. bolletii BCRC 16915, M. abscessus subsp. massiliense BCRC 16916, M. chelonae ATCC 35752, and M. peregrinum ATCC 700686. Significant synergism, classified by an FICI of ≤0.5, was demonstrated for the combinations of rifabutin and imipenem in 100% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates, and significant synergism for rifabutin and tigecycline was demonstrated in 77% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates. Among the 6 clarithromycin-resistant (MICs ≥ 8 mg/liter) M. abscessus subsp. abscessus isolates, the combination of rifabutin and clarithromycin was 100% synergistic. Rifabutin showed promising in vitro synergism with first-line anti-M. abscessus agents, especially for macrolide-resistant M. abscessus subsp. abscessus isolates.

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