Importance of Lipophilicity and Polar Surface Area of Compounds on the Transport Activity of Intestinal H&lt;sup&gt;+&lt;/sup&gt;/tertiary Amine Antiporter

Ishida, Kazuya; Horie, Asuka; Matsuba, Emi; Watanabe, Yuri; Fukao, Miki; Hashimoto, Yoshiaki

doi:10.5649/jjphcs.41.236

Cited by 2 publications

(2 citation statements)

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“…Regularly, nitro Mannich bases are dynamic substances in some outstanding arrangements having a place with various gatherings of medications that are ordered by their pharmacological potencies . The main feature of these classes is the presence of the polar nitro group that cause a decrease in the lipophilicity of the drug . Numerous nitro compounds are dynamic substances in many active drugs that proved their pharmacological activities, for instance the antiulcer drugs containing the nitro group in their structure ranitidine and nizatidine, (Figure ) .…”

Section: Introductionmentioning

confidence: 99%

“…[9] The main feature of these classes is the presence of the polar nitro group that cause a decrease in the lipophilicity of the drug. [10] Numerous nitro compounds are dynamic substances in many active drugs that proved their pharmacological activities, for instance the antiulcer drugs containing the nitro group in their structure ranitidine and nizatidine, ( Figure 2). [11,12] In addition, the veterinary medications such as nitenpyram (Nitrol), (Figure 2), which is power insecticides for rapid killing external parasites of dogs and cats, such as fleas.…”

Section: Introductionmentioning

confidence: 99%

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Novel Pyruvate Kinase (PK) Inhibitors: New Target to Overcome Bacterial Resistance

et al. 2020

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In the present investigation, some novel nitro Mannich bases derived from Michael type addition of activated nitro olefin, β‐nitrostyrene with various amines either primary or secondary including some amino sugars were designed and synthesized. The produced Mannich bases have been full characterized through different spectroscopic techniques. Antimicrobial evaluation has been performed against the Gram positive S. aureus and methicillin‐resistant S. aurues (MRSA) infections. 5 of the synthesized compounds represent the best candidates in the biological screening, they have exhibited good activity with MIC values range from 100 to 250 μg/ml. The active agents have been tested for pyruvate kinase inhibition activity with % of inhibition range from 30 to 79 % with IC50 in a nano molar range. They also exhibited significant Pyruvate kinase inhibition in nanomolar range with IC50 of 1066, 662, 1887, 418 and 1128 ng/ml, respectively (versus 196 ng/ml for AZD7545). Molecular docking calculations for active agents were performed. A complete conformational analysis molecular modeling utilizing Gaussian 09 program (HF/DFT) was used to verify the mode of bonding through the optimized geometries as well as essential quantum parameters were calculated using frontier energies (EHOMO & ELUMO) for the active candidates indicating the overall stability of the structure.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Pyruvate Kinase (PK) Inhibitors: New Target to Overcome Bacterial Resistance

et al. 2020

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Substrate Specificity of an H<sup>+</sup>/quinidine Antiport System in Human Embryonic Kidney HEK293 Cells

Usami

Hirayama

Koyama

et al. 2018

Jpn. J. Pharm. Health Care Sci.

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We recently found the H + /quinidine (QND) antiport system in canine kidney MDCK and porcine kidney LLC-PK1 cells. The aims of the present study were to confirm the presence of the H + /QND antiport system in human embryonic kidney (HEK) 293 cells, and to investigate the substrate specificity of the system. The cellular uptake of 100 µM QND into HEK293 cells was decreased by acidification of extracellular pH and by NH4Cl-induced alkalization of intracellular pH. In addition, a lipophilic cationic drug, diphenhydramine (DPH), significantly decreased the QND uptake in HEK293 cells. In order to evaluate the substrate specificity of the renal H + /QND antiport system, we investigated the DPH-sensitive uptake (Δuptake) of 12 cationic compounds (celiprolol, acebutolol, procainamide, pindolol, bisoprolol, metoprolol, flecainide, clonidine, pyrilamine, QND, propranolol, and verapamil). The Δuptake positively correlated with their lipophilicity (Log D) values, and negatively correlated with their polar surface area (Log PSA) values. In contrast, the Δuptake did not correlate with their molar volume (MV), molar refractivity (MR), or polarization (PO). These findings indicate that an H + /QND antiport system is present in HEK293 cells, and that the Log D and Log PSA of drugs are important factors responsible for the transport activity of the postulated H + /lipophilic cation antiporter in the kidney.

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Importance of Lipophilicity and Polar Surface Area of Compounds on the Transport Activity of Intestinal H<sup>+</sup>/tertiary Amine Antiporter

Abstract: sensitive uptake (Δuptake) of 12 cationic compounds (celiprolol, acebutolol, pindolol, bisoprolol, metoprolol, propranolol, procainamide, quinidine, flecainide, clonidine, pyrilamine, and verapamil)

Cited by 2 publications

References 13 publications

Novel Pyruvate Kinase (PK) Inhibitors: New Target to Overcome Bacterial Resistance

Novel Pyruvate Kinase (PK) Inhibitors: New Target to Overcome Bacterial Resistance

Substrate Specificity of an H<sup>+</sup>/quinidine Antiport System in Human Embryonic Kidney HEK293 Cells

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