Effect of Aminomethyl (N-Mannich Base) Derivatization on the Ability of S6Acetyloxymethyl-S-Mercaptopurine Prodrug to Deliver 6-Mercaptopurine through Hairless Mouse Skin

Saab, Akram N.; Sloan, Kenneth B.; Beall, Howard D.; Villanueva, René

doi:10.1002/jps.2600791212

Cited by 13 publications

(8 citation statements)

References 21 publications

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“…The hydrophilic properties of a drug can be further enhanced by its solubility in water, quaternization of the nitrogen atom in the aminomethyl derivative and conversion to an ammonium salt. 11 This information was found appropriate with our results.…”

Section: In Vitro Antimicrobial Activitiessupporting

confidence: 83%

Synthesis and biological evaluation of some 4-amino-3-mercapto-1,2,4-triazoles bearing mannich base

Dündar¹,

Kaynak-Onurdag²,

Önkol³

2019

Bioorg. Med. Chem. Rep.

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Bacterial and fungal resistance to almost all antimicrobial agents have been observed in disease causing bacteria and fungi. A series of 3-({4-[substitutedbenzylideneamino]-1-(morpholin-4-ylmethyl)-5-thioxo-4,5dihydro-1H-1,2,4-triazol-3-yl}methyl)-2(3H)-benzothiazolone (6a-6g) were prepared by the reaction of morpholine in the presence of formaldehyde using microwave irradiation with the yield ranging from 50% to 98%. The newly synthesized compounds were characterized on the basis of elemental analysis, IR and 1 H-NMR. All the synthesized compounds were tested for their antibacterial activities against Gram + and Grambacteria, their clinical isolates and antifungal activities against Candida species in vitro. Many of these compounds exhibited potent antifungal activity with MIC values in the range (MIC: 32-64 µg/mL), while compound 6g (MIC: 32 µg/mL) had comparable activity with ampicillin and gentamycin (MIC: 4 µg/mL) against E.faecalis isolate

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Section: In Vitro Antimicrobial Activitiessupporting

confidence: 83%

Synthesis and biological evaluation of some 4-amino-3-mercapto-1,2,4-triazoles bearing mannich base

Dündar¹,

Kaynak-Onurdag²,

Önkol³

2019

Bioorg. Med. Chem. Rep.

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“…Dopamine receptors are G protein-coupled receptors that are widely distributed in the brain, and whose primary endogenous ligand is the neurotransmitter dopamine. There are at least five subtypes of dopamine receptors, but D 1-2 receptor subtypes usually predominate, as they are 10e100 times more numerous than D [3][4][5] subtypes.…”

Section: Ligands Of Dopamine Receptorsmentioning

confidence: 99%

“…The solubility in water of a drug could be further enhanced through the quaternization of the nitrogen atom in its aminomethyl derivative and conversion into an ammonium salt. Alternatively, the lipophilic properties of a drug could be tailored through a Mannich reaction if the appropriate amine reagent is employed [5]. In addition, the aminomethylated drugs could act as prodrugs, releasing the active substance under controlled hydrolytic conditions via deaminomethylation [6] or deamination [7].…”

Section: Introductionmentioning

confidence: 99%

Mannich bases in medicinal chemistry and drug design

Roman¹

2015

European Journal of Medicinal Chemistry

282

110

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The biological activity of Mannich bases, a structurally heterogeneous class of chemical compounds that are generated from various substrates through the introduction of an aminomethyl function by means of the Mannich reaction, is surveyed, with emphasis on the relationship between structure and biological activity. The review covers extensively the literature reports that have disclosed Mannich bases as anticancer and cytotoxic agents, or compounds with potential antibacterial and antifungal activity in the last decade. The most relevant studies on the activity of Mannich bases as antimycobacterial agents, antimalarials, or antiviral candidates have been included as well. The review contains also a thorough coverage of anticonvulsant, anti-inflammatory, analgesic and antioxidant activities of Mannich bases. In addition, several minor biological activities of Mannich bases, such as their ability to regulate blood pressure or inhibit platelet aggregation, their antiparasitic and anti-ulcer effects, as well as their use as agents for the treatment of mental disorders have been presented. The review gives in the end a brief overview of the potential of Mannich bases as inhibitors of various enzymes or ligands for several receptors.

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“…15 Solubility of the Mannich bases in water could be further increased as a result of their protonation to form the respective ammonium salts. 16 They can also act as prodrugs forming reactive derivatives via deaminomethylation or deamination processes. 17 It is therefore no surprise that Mannich reaction has become a Vol.…”

Section: Introductionmentioning

confidence: 99%

Study of Reactions of Two Mannich Bases Derived of 4’-Hydroxychalcones with Glutathione by RP‑TLC, RP‑HPLC and RP‑HPLC‑ESI‑MS Analysis

Bernardes¹,

Pérez²,

Mayer³

et al. 2016

J. Braz. Chem. Soc.

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4'-Hydroxychalcones have been reported to possess several beneficial biological effects. Several lines of evidence accumulated to demonstrate increased biological activities of the Mannich base derivatives of the parent 4'-hydroxychalcones. Bioactivities of chalcones and related α,β-unsaturated ketones are frequently associated with their reactivity with cellular thiols, such as GSH. For comparison of GSH reactivity, two bis Mannich bases of two 4'-hydroxychalcones were synthesized and reacted with GSH under non-cellular conditions. Reversed-phase thin layer chromatography (RP-TLC) and reversed-phase high performance liquid chromatography (RP-HPLC) analysis showed formation of two polar products which structures were confirmed by RP-HPLC-ESI-MS (RP-HPLC-electrospray ionization mass spectrometry) as 1:1 chalcone-GSH adducts in each case. At pH values below 8.0, the two bis Mannich bases showed higher GSH reactivity than two 4'-hydroxychalcones. Influence of the nature of the amino groups, the ring-B substituents and pH of the medium on reactivity was also investigated. The findings could serve as useful structure-activity information for subsequent molecular modification of thiol-reactive 4'-hydroxychalcones.

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Effect of Aminomethyl (N-Mannich Base) Derivatization on the Ability of S6Acetyloxymethyl-S-Mercaptopurine Prodrug to Deliver 6-Mercaptopurine through Hairless Mouse Skin

Cited by 13 publications

References 21 publications

Synthesis and biological evaluation of some 4-amino-3-mercapto-1,2,4-triazoles bearing mannich base

Synthesis and biological evaluation of some 4-amino-3-mercapto-1,2,4-triazoles bearing mannich base

Mannich bases in medicinal chemistry and drug design

Study of Reactions of Two Mannich Bases Derived of 4’-Hydroxychalcones with Glutathione by RP‑TLC, RP‑HPLC and RP‑HPLC‑ESI‑MS Analysis

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