α-Amino acid derivatives as proton pump inhibitors and potent anti-ulcer agents

Sharma, Preeti; Singh, S. P.; Siddiqui, T. I.; Singh, Vijay; Kundu, Bijoy; Prathipati, Philip; Saxena, Anil Kumar; Dikshit, Dinesh K.; Rastogi, Leena; Dixit, Chetna; Gupta, MB; Patnaik, G. K.; Dikshit, Madhu

doi:10.1016/j.ejmech.2006.08.016

Cited by 16 publications

(7 citation statements)

References 22 publications

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“…5-Hydroxy-1,3-oxazoles exist in their corresponding keto tautomer: 1,3-oxazol-5(4H)-ones which present cytotoxic [9,10], antiviral [11], plant growth regulating properties [12]. Some representants of N-acyl-α-amino acids class show biological activities, such as antihypertensive [13], anticancer [14], mucolytic [15], antianaemic [16], anti-ulcer effect [17], and are specific antidotes in acute intoxications [18,19]. N-Acyl-αamino-ketones display anti-inflammatory [20], antiviral [21,22] and antithrombotic action [23].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Cytotoxicity Assessment of New 4-Benzyl-1,3-Oxazole Derivatives Incorporating 4-[(4-Bromophenyl)sulfonyl]phenyl Fragment

Apostol¹

2021

FARMACIA

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Herein we present the design, synthesis, characterization, and cytotoxicity assessment of seven compounds derived from phenylalanine that incorporate a 4-[(4-bromophenyl)sulfonyl]phenyl fragment: four open-chain products (one N-acyl-α-amino acid, one N-acyl-α-amino acyl chloride, two N-acyl-α-amino ketones), and three five-membered heterocycles with two heteroatoms (O and N): one 2-aryl-4-benzyl-1,3-oxazol-5(4H)-one, and two 2-aryl-4-benzyl-1,3-oxazoles with p-tolyl, and m-xylyl substituent, respectively, in position 5. Structures of new derivatives were assigned by elemental analysis, NMR spectroscopy, and other spectral methods (FT-IR, MS, UV-Vis). Evaluation of the purity of the compounds was realized by reversed-phase highperformance liquid chromatography. Daphnia magna toxicological test was used to assess the cytotoxicity of new compounds. RezumatStudiul prezintă proiectarea, sinteza, caracterizarea și evaluarea citotoxicității a șapte compuși derivați de la fenilalanină, care incorporează un fragment 4-[(4-bromofenil)sulfonil]fenil: patru produși cu catenă deschisă (N-acil-α-aminoacid, o clorură de Nacil-α-aminoacil, două N-acil-α-aminocetone) și trei heterocicluri pentaatomice cu doi heteroatomi (O și N): o 2-aril-4-benzil-1,3-oxazol-5(4H)-onă și 2-aril-4-benzil-1,3-oxazoli cu substituentul p-tolil și respectiv, m-xilil, în poziția 5. Structurile noilor derivați au fost atribuite prin analiză elementală, spectroscopie RMN și alte metode spectrale (FT-IR, SM, UV-Viz). Evaluarea purității compușilor a fost realizată prin cromatografie de lichide de înaltă performanţă cu fază inversă. Testul toxicologic Daphnia magna a fost utilizat pentru a se evalua citotoxicitatea noilor compuși.

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Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Cytotoxicity Assessment of New 4-Benzyl-1,3-Oxazole Derivatives Incorporating 4-[(4-Bromophenyl)sulfonyl]phenyl Fragment

Apostol¹

2021

FARMACIA

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“…On the same two series of 2-guanidinothiazoles (4,5, Scheme 1), Borges and Takahata also reported from their two consecutive studies [15,16] that the electronic properties of compounds such as dipole moment and charges at some atoms, are important for their activity. On a fairly large series of -amino acid derivatives, a QSAR study performed by Sharma et al [17] also suggested that their PPI inhibition activity is controlled by the electronic properties, such as the energy of the highest occupied molecular orbital ( HOMO ), H-bond formation ability of some groups, and steric factors. A series of 179 quinoline and quinazoline heterocyclic analogues exhibiting inhibitory activity against H + ,K + -ATPase were investigated by comparative molecular �eld analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) by Nayana et al [18] to �nd that in addition to electrostatic and steric �elds, hydrophobic and H-bond donor and acceptor �elds were also important for the H + ,K + -ATPase inhibition activity of these compounds.…”

Section: Introductionmentioning

confidence: 99%

A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a Series of Biaryl Imidazole Derivatives Acting as H⁺/K⁺-ATPase Inhibitors

Agarwal¹,

Bajpai²,

Srivastava³

et al. 2013

Structural Biology

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The H+/K+-ATPase or proton pump is a magnesium-dependant enzyme which causes the exchange of a proton against a potassium ion through a membrane. Over activity of this enzyme causes hyperacidity by producing more of hydrochloric acid inside the stomach. This enzyme, therefore, has been found to be a good target for designing compounds to treat hyperacidity. A quantitative structure-activity relationship (QSAR) study has been made on a novel series of biaryl imidazole derivatives acting as H+/K+-ATPase inhibitors. The H+/K+-ATPase inhibition activity of these compounds is found to be significantly correlated with global topological charge indices (GTCIs) and the total polar surface area (TPSA) of the molecules, indicating the involvement of strong electronic interaction between the molecule and the receptor. Based on the correlations obtained, some new H+/K+-ATPase inhibitors are predicted. The docking studies of these predicted compounds exhibit that these compounds will have even better interaction with the receptor than those already marketed. Thus, they can prove more potent drugs for the treatment of hyperacidity.

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“…On the same two series of 2-guanidinothiazoles ( 4 , 5 , Figure 6), Grünheidt and Takahata also reported in their two consecutive studies [16, 17] that the electronic properties of compounds such as dipole moment and charges at some atoms are important for their activity. On a fairly large series of α -amino acid derivatives, a QSAR study performed by Sharma et al [18] also suggested that their PPI inhibition activity is controlled by the electronic properties, such as the energy of the highest occupied molecular orbital ( E HOMO ), H-bond formation ability of some groups, and steric factors. A series of 179 quinoline and quinazoline heterocyclic analogues exhibiting inhibitory activity against H + /K + -ATPase was investigated by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) by Nayana et al [3] to find that in addition to electrostatic and steric fields, hydrophobic and H-bond donor and acceptor fields were also important for the H + /K + -ATPase inhibition activity of these compounds.…”

Section: Introductionmentioning

confidence: 99%

A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a Series of Heteroaryl- and Heterocyclyl-Substituted Imidazo[1,2-a]Pyridine Derivatives Acting as Acid Pump Antagonists

Agarwal¹,

Bajpai²,

Gupta³

2013

Biochemistry Research International

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A quantitative structure-activity relationship (QSAR) and molecular docking study has been performed on a series of heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]pyridine derivatives acting as acid pump antagonists in order to have a better understanding of the mechanism of H+/K+-ATPase inhibition. The QSAR study shows a significant correlation of activity with Global Topological Charge Indices (GTCI) of the compounds and the hydrophobic constant π of some substituents, indicating that the charge transfer within the molecule and the hydrophobic property of some substituents will be the controlling factor of the activity of these compounds and that there can be dispersion interaction between the molecules and the receptor, where some substituents may have hydrophobic interaction, too. Based on this correlation some new compounds with higher potency have been predicted and their docking study has been performed to see if they can have better interaction with the receptor. The ADME properties of these predicted compounds have also been reported that follow Lipinski's rule of five.

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α-Amino acid derivatives as proton pump inhibitors and potent anti-ulcer agents

Cited by 16 publications

References 22 publications

Synthesis, Characterization, and Cytotoxicity Assessment of New 4-Benzyl-1,3-Oxazole Derivatives Incorporating 4-[(4-Bromophenyl)sulfonyl]phenyl Fragment

Synthesis, Characterization, and Cytotoxicity Assessment of New 4-Benzyl-1,3-Oxazole Derivatives Incorporating 4-[(4-Bromophenyl)sulfonyl]phenyl Fragment

A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a Series of Biaryl Imidazole Derivatives Acting as H⁺/K⁺-ATPase Inhibitors

A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a Series of Heteroaryl- and Heterocyclyl-Substituted Imidazo[1,2-a]Pyridine Derivatives Acting as Acid Pump Antagonists

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α-Amino acid derivatives as proton pump inhibitors and potent anti-ulcer agents

Cited by 16 publications

References 22 publications

Synthesis, Characterization, and Cytotoxicity Assessment of New 4-Benzyl-1,3-Oxazole Derivatives Incorporating 4-[(4-Bromophenyl)sulfonyl]phenyl Fragment

Synthesis, Characterization, and Cytotoxicity Assessment of New 4-Benzyl-1,3-Oxazole Derivatives Incorporating 4-[(4-Bromophenyl)sulfonyl]phenyl Fragment

A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a Series of Biaryl Imidazole Derivatives Acting as H+/K+-ATPase Inhibitors

A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a Series of Heteroaryl- and Heterocyclyl-Substituted Imidazo[1,2-a]Pyridine Derivatives Acting as Acid Pump Antagonists

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A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a Series of Biaryl Imidazole Derivatives Acting as H⁺/K⁺-ATPase Inhibitors