Binding Optimization through Coordination Chemistry: CXCR4 Chemokine Receptor Antagonists from Ultrarigid Metal Complexes

Khan, Abid; Nicholson, Gary; Greenman, John; Madden, Leigh A.; McRobbie, Graeme; Pannecouque, Christophe; Clercq, Erik De; Ullom, Robert; Maples, Danny L.; Maples, Randall D.; Silversides, Jon D.; Hubin, Timothy J.; Archibald, Stephen J.

doi:10.1021/ja807921k

Cited by 79 publications

(96 citation statements)

References 16 publications

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“…The synthesis of some of the cross-bridged tetraazamacrocycle mono-and bisligands, precursors, and complexes (compounds 1 to 18) was conducted on the basis of methods described in the literature (29,33,34,39 Archibald, submitted for publication). The mono-and bisquinoline derivatives of macrocyclic polyamines (compounds 19 to 26) were synthesized and purified by chromatography and/or solvent crystallization according to the methods that we described earlier (22,30) and were recovered in moderate to good yields.…”

Section: Discussionmentioning

confidence: 99%

“…The synthesis of the ligand (L2) was conducted according to methods described in the literature (29). In a glove box with an inert atmosphere, 0.330 g (0.001 mol) of L2 and 0.127 g (0.001 mol) of anhydrous FeCl 2 (Aldrich) were stirred in 20 ml anhydrous dimethylformamide (DMF) for 1 week.…”

Section: Synthesis Of Complex Fe(l2)cl 2 (Compound 9)mentioning

confidence: 99%

“…Within the past decade, these macrocycles have become important structural moieties for a variety of diagnostic and therapeutic pharmaceutical agents (21). Our group has been actively involved in the synthesis of these macrocyclic polyamines and their metal complexes and demonstrated their activities against HIV through CXCR4 inhibition (22)(23)(24)(25)(26)(27). We have recently employed the metal coordination approach to prepare a series of metal complexes using cross-bridged and side-bridged tetraazamacrocyclic ligands and have shown that both the ligands and their metal complexes are effective antimalarial agents (22,28).…”

mentioning

confidence: 99%

“…1) for their activities against S. mansoni in vitro and in vivo and present here our findings on their antischistosomal activity. Seven of these 26 compounds (compounds 8, 9, 15 to 17, 20, and 21) are newly described in this report, and for the other compounds, either their antiviral or antimalarial activities have been described previously or they have been submitted elsewhere for synthetic method development and/or to report their antiviral or antimalarial activities (21)(22)(23)(24)(25)(26)(27)(28)(29)(30).…”

mentioning

confidence: 99%

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Discovery of Antischistosomal Drug Leads Based on Tetraazamacrocyclic Derivatives and Their Metal Complexes

Khan

Keiser

Amoyaw

et al. 2016

Antimicrob Agents Chemother

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Section: Discussionmentioning

confidence: 99%

Section: Synthesis Of Complex Fe(l2)cl 2 (Compound 9)mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Discovery of Antischistosomal Drug Leads Based on Tetraazamacrocyclic Derivatives and Their Metal Complexes

Khan

Keiser

Amoyaw

et al. 2016

Antimicrob Agents Chemother

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“…The interaction of the metallodrug has been optimized by using ultra rigid chelator units that offer an equatorial site for coordination to the amino acid side chains of the protein. 6 Cu 2 -xylyl-bicyclam also exhibits anti-HIV activity. It was used Cu 2+ -cyclam as a paramagnetic probe to investigate interactions of metal-locyclams with the model protein target in solution.…”

Section: Copper For Antiviral Hiv Activitymentioning

confidence: 99%

Synthesis of Metal-Organic (Complexes) Compounds Copper(ii)-Imidazole for Antiviral Hiv Candidate

Sucipto

Martak

2016

IJTID

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The human immunodeficiency virus (HIV) is viruses known as rotaviruses. Potential target for therapeutic is reverse transcriptase (RT), possesses an RNA-dependent DNA polymerase, DNA-dependent DNA polymerase and ribonuclease H fuctions. Imidazoles have high anti-HIV inhibitory activity, some derivates of imidazole reported drugs . 8-chloro-2,3-dihydroimidazole[1,2-b] [1,4,2]benzodithiazine-5,5-dioxides and 9-chloro-2,3,4-trihydropyri-mido[1,2-b] Key words: Complexes compound, copper, imidazole, antiviral, HIV ABSTRAK Human immunodeficiency virus (HIV) adalah virus yang termasuk golongan rotavirus. Target potensial untuk terapi adalah reverse transcriptase (RT), memiliki sebuah DNA-dependent RNA polimerase, DNA-dependent DNA polimerase dan ribonuklease. Imidazol memiliki aktivitas penghambatan anti-HIV yang tinggi, beberapa turunan dari imidazol melaporkan obat. 8-kloro-2,3-dihydroimidazole [1,2-b] [1,4,2] benzodithi-azine-5,5-dioksida dan 9-chloro-2,3,4-trihydropyri-mido [1,2-b]

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Vanadium, Copper and Zinc in Medicine

Dabrowiak

2009

Metals in Medicine

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The first report of the use of vanadium for the treatment of diabetes mellitus (DM) was published by the French physician Dr. B. Lyonnet, who in 1899 described the ability of the simple vanadium compound sodium vanadate, Na 3 VO 4 (Figure 7.1), to lower the blood sugar levels of diabetic patients [1]. More than 80 years later, both vanadate and the related ion, vanadyl, VO 2þ (Figure 7.1), were shown to exhibit insulin-mimetic effects on the oxidation of glucose in adipocytes (fat cells) of rats [2][3][4], and sodium vanadate was found to be effective in controlling blood glucose levels and reducing cardiac decline in diabetic rats [5]. These early reports led to the synthesis and study of a large number of vanadium-based insulin-mimetic agents, a few of which are shown in Figure 7.1 [6][7][8][9][10][11][12][13][14]. One of these compounds, bis(ethylmaltolato)oxovanadium(IV), BEOV, is currently in phase II clinical trials in the United States as a potential new insulin-mimetic agent for treating diabetes.Vanadium, element 23, is found in low concentrations in the body ($100 mg total) and its function is not known. While vanadium has many oxidation states, those commonly found in the biological system and incorporated into vanadium complexes for treating diabetes are V þ5 , which has the electronic configuration [Ar]3d 0 , and V þ4 , with the configuration [Ar]3d 1 . The formula for vanadate ion is VO 4 À3 , but since the pK a s for the first and second protonation of the ion are $13 and $8 respectively, at neutral pH in dilute solution the ion exists mainly in its diprotonated form, [H 2 VO 4 ] À (Figure 7.1). Since vanadate is isostructural and isoelectronic with phosphate but cannot undergo the same chemical reactions as phosohate, vanadate is often used as an inhibitor in mechanistic studies of biochemical reactions that require phosphate. Like phosphate, vanadate can also form higher-order structures, but vanadate has a stronger tendency to nucleate and can form species that contain up to 10 vanadium ions, such as decavanadate, [V 10 O 28 ] 6À [15].The simplest ion in water at neutral pH for aquated V þ4 is [VO(OH)(H 2 O) 4 ] þ , which since it contains a VO 2þ species is often referred to simply as vanadyl. This octahedral complex contains an oxo ligand (O 2À ), a hydroxo group (OH À ) and four bound water molecules. Depending on the concentration of vanadium and the pH of the medium, vanadyl can also form higher-order multinuclear structures in solution. The water exchange rate constant for [VO(OH)(H 2 O) 4 ] þ at 25 C is k $ 5 Â 10 2 s À1 (Figure 1.20) [16].Complexes containing V þ5 are diamagnetic (S ¼ 0). Since the main isotope, 51 V, is NMR 'active' (I ¼ 7/2) and has high natural abundance (>99%), compounds containing V þ5 can easily be studied using NMR. Mononuclear vanadyl complexes are paramagnetic with one unpaired electron -that is, S ¼ 1 / 2 -and, although Metals in MedicineJames C. Dabrowiak not studied with NMR, they can be investigated using electron paramagnetic resonance (EPR) see (Box 7.1). ...

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Binding Optimization through Coordination Chemistry: CXCR4 Chemokine Receptor Antagonists from Ultrarigid Metal Complexes

Cited by 79 publications

References 16 publications

Discovery of Antischistosomal Drug Leads Based on Tetraazamacrocyclic Derivatives and Their Metal Complexes

Discovery of Antischistosomal Drug Leads Based on Tetraazamacrocyclic Derivatives and Their Metal Complexes

Synthesis of Metal-Organic (Complexes) Compounds Copper(ii)-Imidazole for Antiviral Hiv Candidate

Vanadium, Copper and Zinc in Medicine

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