Preliminary in vitro Studies on Two Potent, Water-Soluble Trimethoprim Analogues with Exceptional Species Selectivity Against Dihydrofolate Reductase from Pneumocystis carinii and Mycobacterium avium.

ChemInform ◽  
2004 ◽  
Vol 35 (37) ◽  
Author(s):  
Ronald A. Forsch ◽  
Sherry F. Queener ◽  
Andre Rosowsky
Keyword(s):  
Dihydrofolate Reductase ◽  
Mycobacterium Avium ◽  
Pneumocystis Carinii ◽  
Water Soluble ◽  
In Vitro Studies ◽  
Species Selectivity

scholarly journals Antibacterial activities of epiroprim, a new dihydrofolate reductase inhibitor, alone and in combination with dapsone.

1996 ◽  
Vol 40 (6) ◽  
pp. 1376-1381 ◽  
Author(s):  
H H Locher ◽  
H Schlunegger ◽  
P G Hartman ◽  
P Angehrn ◽  
R L Then
Keyword(s):  
Dihydrofolate Reductase ◽  
Biological Fluids ◽  
Pneumocystis Carinii ◽  
Antibacterial Activities ◽  
Gram Negative Bacteria ◽  
Highly Active ◽  
Excellent Activity ◽  
Resistant Strains ◽  
Better Than

Epiroprim (EPM; Ro 11-8958) is a new selective inhibitor of microbial dihydrofolate reductase. EPM displayed excellent activity against staphylococci, enterococci, pneumococci, and streptococci which was considerably better than that of trimethoprim (TMP). EPM was also active against TMP-resistant strains, although the MICs were still relatively high. Its combination with dapsone (DDS) was synergistic and showed as in vitro activity superior to that of the TMP combination with sulfamethoxazole (SMZ). The EPM-DDS (ratio, 1:19) combination inhibited more than 90% of all important gram-positive pathogens at a concentration of 2 + 38 micrograms/ml. Only a few highly TMP-resistant staphylococci and enterococci were not inhibited. EPM was also more active than TMP against Moraxella catarrhalis, Neisseria meningitidis, and Bacteroides spp., but it was less active than TMP against all other gram-negative bacteria tested. Atypical mycobacteria were poorly susceptible to EPM, but the combination with DDS was synergistic and active at concentrations most probably achievable in biological fluids (MICs from 0.25 +/- 4.75 to 4 + 76 micrograms/ml). EPM and the EPM-DDS combination were also highly active against experimental staphylococcal infections in a mouse septicemia model. The combination EPM-DDS has previously been shown to exhibit activity in Pneumocystis carinii and Toxoplasma models and, as shown in the present study, also shows good activity against a broad range of bacteria including many strains resistant to TMP and TMP-SMZ.

scholarly journals In Vitro Activities of Several Diaminomethylpyridopyrimidines against Mycobacterium avium Complex

1998 ◽  
Vol 42 (12) ◽  
pp. 3315-3316 ◽  
Author(s):  
Carolyn M. Shoen ◽  
Olga Choromanska ◽  
Robert C. Reynolds ◽  
James R. Piper ◽  
Cheryl A. Johnson ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Dhfr Inhibitors ◽  
Better Than

ABSTRACT Three recently synthesized dihydrofolate reductase (DHFR) inhibitors designated SoRI 8890, 8895, and 8897 were evaluated for their in vitro activities against 25 isolates of Mycobacterium avium complex. The MICs at which 50 and 90% of isolates were inhibited were 1 and 2, 4 and 8, and 4 and 8 μg/ml for SoRI 8890, 8895, and 8897, respectively. Although the addition of dapsone at 0.5 μg/ml did not significantly enhance the in vitro activities of these compounds, their activities alone were comparable to, if not better than, results seen with other DHFR inhibitors, such as pyrimethamine or WR99210.

scholarly journals Water-Soluble Cuprizone Derivative: Synthesis, Characterization, and in Vitro Studies

ACS Omega ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 1685-1689 ◽  
Author(s):  
Martin Fries ◽  
Meike Mertens ◽  
Nico Teske ◽  
Markus Kipp ◽  
Cordian Beyer ◽  
...  
Keyword(s):  
Water Soluble ◽  
In Vitro Studies

Water-soluble octahedral molybdenum cluster compounds Na2[Mo6I8(N3)6] and Na2[Mo6I8(NCS)6]: Syntheses, luminescence, and in vitro studies

2016 ◽  
Vol 441 ◽  
pp. 42-49 ◽  
Author(s):  
Kaplan Kirakci ◽  
Pavel Kubát ◽  
Monika Kučeráková ◽  
Václav Šícha ◽  
Helena Gbelcová ◽  
...  
Keyword(s):  
Water Soluble ◽  
In Vitro Studies ◽  
Cluster Compounds ◽  
Molybdenum Cluster

scholarly journals Identification of New Compounds with Anticonvulsant and Antinociceptive Properties in a Group of 3-substituted (2,5-dioxo-pyrrolidin-1-yl)(phenyl)-Acetamides

2021 ◽  
Vol 22 (23) ◽  
pp. 13092
Author(s):  
Michał Abram ◽  
Marcin Jakubiec ◽  
Anna Rapacz ◽  
Szczepan Mogilski ◽  
Gniewomir Latacz ◽  
...  
Keyword(s):  
Water Soluble ◽  
Calcium Currents ◽  
In Vitro Studies ◽  
Maximal Electroshock ◽  
Induction Effect ◽  
Potential Candidate ◽  
Seizure Models ◽  
Seizure Model

We report herein a series of water-soluble analogues of previously described anticonvulsants and their detailed in vivo and in vitro characterization. The majority of these compounds demonstrated broad-spectrum anticonvulsant properties in animal seizure models, including the maximal electroshock (MES) test, the pentylenetetrazole-induced seizure model (scPTZ), and the psychomotor 6 Hz (32 mA) seizure model in mice. Compound 14 showed the most robust anticonvulsant activity (ED50 MES = 49.6 mg/kg, ED50 6 Hz (32 mA) = 31.3 mg/kg, ED50scPTZ = 67.4 mg/kg). Notably, it was also effective in the 6 Hz (44 mA) model of drug-resistant epilepsy (ED50 = 63.2 mg/kg). Apart from favorable anticonvulsant properties, compound 14 revealed a high efficacy against pain responses in the formalin-induced tonic pain, the capsaicin-induced neurogenic pain, as well as in the oxaliplatin-induced neuropathic pain in mice. Moreover, compound 14 showed distinct anti-inflammatory activity in the model of carrageenan-induced aseptic inflammation. The mechanism of action of compound 14 is likely complex and may result from the inhibition of peripheral and central sodium and calcium currents, as well as the TRPV1 receptor antagonism as observed in the in vitro studies. This lead compound also revealed beneficial in vitro ADME-Tox properties and an in vivo pharmacokinetic profile, making it a potential candidate for future preclinical development. Interestingly, the in vitro studies also showed a favorable induction effect of compound 14 on the viability of neuroblastoma SH-SY5Y cells.

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