Amiloride Conformation: The Effect of Different Crystalline Environments

Żesławska, Ewa; Oleksyn, Barbara J.; Stadnicka, Katarzyna

doi:10.1007/s11224-004-0731-2

Cited by 11 publications

(8 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All drug molecules and coformer have several binding sites of different acidity/basicity capable of participating in hydrogen-bonding systems and proton transfer, while their planar skeletons are predisposed for potential stacking interactions in these systems. The results of this study contribute to the quite limited crystallographic data available in the CSD (CSD version 5.38 updates Feb 2017) for ALP − and AMI − drugs.…”

Section: Introductionmentioning

confidence: 83%

Adducts of N-Heterocyclic Drugs, Niacin, Allopurinol, and Amiloride, with 2,4-Pyridinedicarboxylic Acid Coformer

Bejagam

Fonarı

Аверкиев

et al. 2017

Crystal Growth & Design

View full text Add to dashboard Cite

A co-crystallization of three drug molecules, niacin (3-pyridine-carboxylic acid = NIA), allopurinol (pyrazolo(3,4-d)pyrimidin-4-one = ALP), and amiloride (3,5-diamino-6-chloro-pyrazine-2-carbonyl)-guanidine = AMI), with the same coformer, 2,4-pyridinedicarboxylic acid (PDA), resulted in three new crystalline products, (NIA)(PDA) (1), (ALP)2(PDA)·1.5H2O (2), and (AMI)2(PDA)2(H2O)2 (3). The formation of new phases was confirmed by IR spectra and X-ray single-crystal and powder diffraction analysis. The proton transfer resulted in the zwitterionic co-crystal 1. In co-crystal 2, neutral ALP molecules existed in the oxo-tautomeric form. Compound 3 crystallizes as the salt with the guanidinium cationic part as in the started amiloride hydrochloride hydrate, and the PDA coformer as the zwitterionic pyridinium dicarboxylate anion. Thus, the diversity of the PDA coformer ionization states included the neutral, zwitterion, and zwitterion anionic forms. All compounds were layered structures where the heterocyclic molecules were linked in the H-bonded corrugated layers stabilized by the diverse conventional and charge-assisted hydrogen bonds with π–π stacking interactions between the layers supported by the mediated water molecules in 2 and 3.

show abstract

Section: Introductionmentioning

confidence: 83%

Adducts of N-Heterocyclic Drugs, Niacin, Allopurinol, and Amiloride, with 2,4-Pyridinedicarboxylic Acid Coformer

Bejagam

Fonarı

Аверкиев

et al. 2017

Crystal Growth & Design

View full text Add to dashboard Cite

show abstract

“…1(b)), the presence of a carbonyl group as intramolecular H‐bond acceptor often enables the assignment of the two amino groups without the need for any additional receptor in order to reduce exchange. This has been shown, e.g., in the conformational investigation of amiloride,15 one of the most prominent acylguanidines in the literature 16–20. The application of cryo‐solvents allowed freezing the rotation around the bond between the central guanidine carbon (C G ) and the acylated nitrogen.…”

Section: Introductionmentioning

confidence: 96%

Chemical shift assignment and conformational analysis of monoalkylated acylguanidines

Kleinmaier

Gschwind

2010

Magnetic Reson in Chemistry

View full text Add to dashboard Cite

Monoalkylated acylguanidines are important functional groups in many biologically active compounds and additionally applied in coordination chemistry. Yet a straightforward assignment of the individual NH chemical shifts and the acylguanidine conformations is still missing. Therefore, in this study, NMR spectroscopic approaches for the chemical and especially the conformational assignment of protonated monoalkylated acylguanidines are presented. While NOESY and (3)J(H, H) scalar couplings cannot be applied successfully for the assignment of acylguanidines, (4)J(H, H) scalar couplings in (1)H,(1)H COSY spectra allow for an unambiguous chemical shift and conformational assignment. It is shown that these (4)J(H, H) long-range couplings between individual acylguanidinium NH resonances are observed solely across all-trans (w) pathways. Already one cis orientation in the magnetisation transfer pathway leads to signal intensities below the actual detection limit and significantly lower than cross-peaks from (2)J(NH, NH) couplings or chemical exchange. However, it should be noted that also in the case of conformational exchange being fast on the NMR time scale, averaged cross-peaks from all-trans (4)J(H, H) scalar couplings are detected, which may lead at first glance to an incomplete or even wrong conformational analysis.

show abstract

“…The crystal structure analysis of salts consisting of two organic compounds is very interesting, since it allows the examination of molecules conformations, especially the search for conformational changes of ionic molecules (Żesławska, Jacob, Sturzebecher, & Oleksyn, 2006;Żesławska, Nitek, & Handzlik, 2017;Żesławska, Nitek, Marona, & Waszkielewicz, 2018;Żesławska, Oleksyn, Fabre, & Benoit-Vical, 2014;Żesławska, Oleksyn, & Stadnicka, 2003;Żesławska, Sturzebecher, & Oleksyn, 2007). The preparation of multicomponent monocrystals suitable for X-ray analysis is a great challenge, but it is worth the effort due the deeper insight into the structural properties coming from X-ray analysis, which provides valuable information about possible conformational changes.…”

Section: Introductionmentioning

confidence: 99%

Pharmacophoric features for a very potent 5‐spirofluorenehydantoin inhibitor of cancer efflux pump ABCB1, based on X‐ray analysis

et al. 2019

Self Cite

View full text Add to dashboard Cite

In order to extend knowledge about pharmacophoric features responsible for ABCB1 inhibitory properties of imidazolidin‐2,4‐dione derivatives, 1′‐[4‐(4‐(o‐methoxyphenyl)‐piperazin‐1‐yl)butyl]‐3′‐methyl‐spiro(fluoren‐9,5′‐imidazolidine)‐2′,4′‐dione (3) and its salt (4) with rhodanine‐3‐acetic acid (RA) were prepared and investigated by X‐ray diffraction method, as well as their efflux modulating effects in cancer cells (mouse T‐lymphoma), cytotoxic and antiproliferative activities were evaluated in vitro. The molecular geometry, intermolecular interactions, and crystal packing of base and acid forms of 3 were analyzed to see, if conformational changes influence the biological activities. The geometry of 2‐methoxyphenylpiperazine and 5‐spirofluorenehydantoin moieties was compared with other crystal structures containing these fragments. Our results indicated a very potent inhibitory action on ABCB1 pump, and significant cytotoxic and antiproliferative properties of 3 in T‐lymphoma, even more potent in the case of multidrug resistance cells. Furthermore, the compound 3 converted into the salt 4 of inactive acid (RA) has maintained both, the efflux pump inhibitory and antiproliferative activities, showing strong synergism with doxorubicin. A comparison of geometry of 3 in both crystal structures (3 and 4) shows a significant difference in the arrangement of piperazine ring with respect to the aliphatic linker.

show abstract

Amiloride Conformation: The Effect of Different Crystalline Environments

Cited by 11 publications

References 28 publications

Adducts of N-Heterocyclic Drugs, Niacin, Allopurinol, and Amiloride, with 2,4-Pyridinedicarboxylic Acid Coformer

Adducts of N-Heterocyclic Drugs, Niacin, Allopurinol, and Amiloride, with 2,4-Pyridinedicarboxylic Acid Coformer

Chemical shift assignment and conformational analysis of monoalkylated acylguanidines

Pharmacophoric features for a very potent 5‐spirofluorenehydantoin inhibitor of cancer efflux pump ABCB1, based on X‐ray analysis

Contact Info

Product

Resources

About