A novel class of highly potent multidrug resistance reversal agents: Disubstituted adamantyl derivatives

Min, Kyung Hoon; Xia, Yan; Kim, Min Jung; Jin, Yinglan; Kaur, Navneet; Kim, Eun Sun; Kim, Dae Kyong; Jung, Hwa Young; Choi, Yongseok; Park, Mi Kyung; Min, Yong Ki; Lee, Kiho; Lee, Kyeong

doi:10.1016/j.bmcl.2009.07.127

Cited by 16 publications

(14 citation statements)

References 11 publications

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“…It makes many potent anticancer drugs ineffective and is largely responsible for the failure of cancer chemotherapy ( Ambudkar et al ., 1999 ). MDR is primarily resulted from the overexpression of ATP-binding cassette (ABC) drug efflux transporters, such as ABCB1 (P-gp), ABCC1-7 (MDR related protein 1–7), and ABCG2 (breast cancer resistance protein) ( Min et al ., 2009 ). These proteins tend to pump out a number of chemically unrelated therapeutic agents ( Min et al ., 2009 ).…”

Section: Introductionmentioning

confidence: 99%

“…MDR is primarily resulted from the overexpression of ATP-binding cassette (ABC) drug efflux transporters, such as ABCB1 (P-gp), ABCC1-7 (MDR related protein 1–7), and ABCG2 (breast cancer resistance protein) ( Min et al ., 2009 ). These proteins tend to pump out a number of chemically unrelated therapeutic agents ( Min et al ., 2009 ). P-gp also transports chemotherapeutic agents to the outside of cells, making the chemotherapy almost ineffective in many cases ( Amin, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

“…Above all, it is considered for P-gp to be clinically more significant than the other transporters, therefore, is viewed as a therapeutic target for MDR cancer cells to respond to anticancer drugs ( Min et al ., 2009 ). Several adamantyl derivatives were synthesized for P-gp inhibitors to overcome MDR using structure-activity relationship (SAR) and cell lines and also assessed in P-gp dependent MDR cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

“…Several adamantyl derivatives were synthesized for P-gp inhibitors to overcome MDR using structure-activity relationship (SAR) and cell lines and also assessed in P-gp dependent MDR cancer cell lines. Many adamantyl derivatives showed potential P-gp inhibitory effect without considerable intrinsic cytotoxicity ( Min et al ., 2009 ). Previously, despite the rigorous efforts, a number of candidates have failed because of their intrinsic toxicities, like verapamil and cyclosporine, and pharmacokinetic interactions in vivo ( Min et al ., 2009 ).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Adamantyl Derivatives on Pharmacokinetic Behavior of Paclitaxel in Rats

Kim

Lee

Jang

et al. 2017

Biomolecules & Therapeutics

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Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioavailability (<5%) due to the Pglycopprotein (P-gp) efflux pump effect. This study investigated in vitro and in vivo P-gp inhibitory effects of adamantyl derivatives AC-603 and AC-786 in rats. Two adamantyl derivatives tested in this study increased the cytotoxicity of daunomycin (DNM) in P-gp overexpressed cell line by inhibiting P-gp efflux function. Pharmacokinetics of PTX with orally co-administered P-gp inhibitors were assessed in rats to improve PTX absorption. The pharmacokinetic parameters of PTX were determined in rats after intravenous (2 mg/kg) or oral (25 mg/kg) administration in the presence or absence of verapamil (a positive control), AC-603 or AC-786 (0.5 mg/kg or 5 mg/kg). Compared to control group (PTX alone), experimental groups (PTX with AC-603 or AC-786) significantly increased the area under the plasma concentration-time curve of PTX following oral administration by 1.7–2.2 fold. The volume of distribution and total clearance of PTX were decreased, while other parameters were not significantly changed. In conclusion, co-administration of AC-603 or AC-786 enhanced the relative bioavailability of orally administered PTX as compared to control.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Adamantyl Derivatives on Pharmacokinetic Behavior of Paclitaxel in Rats

Kim

Lee

Jang

et al. 2017

Biomolecules & Therapeutics

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“…Derivatives of adamantane with nitrogen-containing groups are known to demonstrate antiviral activity, rimantadine being the most well studied among them [1][2][3][4]. Other types of biological activities of adamantane derivatives have also been reported [5][6][7].…”

Section: Introductionmentioning

confidence: 98%

1,3-Bis(1,2,4-triazol-1-yl)adamantane

Marchenko

Potapov

2017

Molbank

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Functional adamantane derivatives are interesting as active pharmaceutical ingredients, building blocks for supramolecular ensembles, and ligands in light of the coordination chemistry of functional materials. In this communication, synthesis of two isomeric 1,3-bis(1,2,4-triazolyl)adamantanes by the reaction of 1,3-dibromoadamantane with 1,2,4-triazole in the absence of solvent is reported. The products, namely 1,3-bis(1,2,4-triazol-1-yl)adamantane and 1-(1,2,4-triazol-1-yl)-3-(1,2,4-triazol-4-yl)adamantane were separated by column chromatography and identified by NMR and mass-spectrometry.

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Enantioselective Desymmetrization of 1,3‐Disubstituted Adamantane Derivatives via Rhodium‐Catalyzed C−H Bond Amination: Access to Optically Active Amino Acids Containing Adamantane Core

Yasue

Yoshida

2021

Adv Synth Catal

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In order to synthesize optically active amino acids containing the adamantane core, an enantioselective desymmetrization of adamantanes via rhodium‐catalyzed C−H bond amination was examined. After investigating various conditions, it was found that the coupling reaction between disubstituted adamantane and aryloxysulfonamide was catalyzed by Rh2(S‐TCPTTL)4 to furnish the desired products having up to 85% ee (e.r.=92.4: 7.6) (>99% ee after recrystallization). The synthetic utility of the enantioenriched products as chiral building blocks was demonstrated by transforming one of them into a dipeptide derivative and a Schiff‐base ligand. The absolute configuration of one of the amino acid derivatives was determined unambiguously by X‐ray single‐crystal structure analysis.

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A novel class of highly potent multidrug resistance reversal agents: Disubstituted adamantyl derivatives

Cited by 16 publications

References 11 publications

Effects of Adamantyl Derivatives on Pharmacokinetic Behavior of Paclitaxel in Rats

Effects of Adamantyl Derivatives on Pharmacokinetic Behavior of Paclitaxel in Rats

1,3-Bis(1,2,4-triazol-1-yl)adamantane

Enantioselective Desymmetrization of 1,3‐Disubstituted Adamantane Derivatives via Rhodium‐Catalyzed C−H Bond Amination: Access to Optically Active Amino Acids Containing Adamantane Core

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