Hydroxyindoles, Indole Alcohols, and Indolethiols

Spande, Thomas F.

doi:10.1002/9780470186947.ch1

Cited by 6 publications

(1 citation statement)

References 639 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is noteworthy that the acidic environment of the stomach fosters the non-enzymatic self-condensation of about 20% I3C to form DIM (Spande, 1979; Stresser et al, 1995). Therefore, DIM could be taken as a direct supplement or indirectly in the form of I3C as a supplement or through I3C-rich cruciferous vegetables.…”

Section: Discussionmentioning

confidence: 99%

Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR

et al. 2015

View full text Add to dashboard Cite

Activation of human pregnane X receptor (hPXR)-regulated expression of cytochrome P450 3A4 (CYP3A4) and multidrug resistance protein 1 (MDR1) plays an important role in mediating adverse drug interactions. Given the common use of natural products as part of adjunct human health behavior, there is a growing concern about natural products for their potential to induce undesired drug interactions through the activation of hPXR-regulated CYP3A4 and MDR1. Here, we studied whether 3,3′-diindolylmethane (DIM), a natural health supplement, could induce hPXR-mediated regulation of CYP3A4 and MDR1 in human hepatocytes and intestinal cells. DIM, at its physiologically relevant concentrations, not only induced hPXR transactivation of CYP3A4 promoter activity but also induced gene expression of CYP3A4 and MDR1. DIM decreased intracellular accumulation of MDR1 substrate rhodamine 123, suggesting that DIM induces the functional expression of MDR1. Pharmacologic inhibition or genetic knockdown of hPXR resulted in attenuation of DIM induced CYP3A4 and MDR1 gene expression, suggesting that DIM induces CYP3A4 and MDR1 in an hPXR-dependent manner. Together, these results support our conclusion that DIM induces hPXR-regulated CYP3A4 and MDR1 gene expression. The inductive effects of DIM on CYP3A4 and MDR1 expression caution the use of DIM in conjunction with other medications metabolized and transported via CYP3A4 and MDR1, respectively.

show abstract

Section: Discussionmentioning

confidence: 99%

Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR

et al. 2015

View full text Add to dashboard Cite

show abstract

New thieno[2,3‐d]pyrimidine derivatives as EGFR^WT and EGFR^T790M inhibitors: Design, synthesis, antiproliferative activities, docking studies, ADMET, toxicity, MD simulation studies

Sobh,

Dahab,

Elkaeed

et al. 2023

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

A series of thieno[2,3‐d]pyrimidines were designed and synthesized as epidermal growth factor receptor (EGFR) inhibitors. These compounds were tested for their ability to inhibit MCF‐7 and A549 cancer cells. The most active compound, 12c, inhibited the growth of both cell lines, with IC50 values of 15.67 and 12.16 μM, respectively. It was found that 12c had inhibitory effects on both EGFRWT and EGFRT790M isoforms, with inhibitory partialities of 37.50 and 148.90 nM, respectively. Additionally, 12c was found to be safer than erlotinib against normal cell lines (IC50 = 38.61 μM). Compound 12c induced early and late apoptosis in A549 cells and arrested cell growth at G1 and G2/M phases. 12c was also found to increase caspases 3 and 8 ratios. Molecular docking indicated the correct binding modes of the synthesized compounds. MD simulations, MM‐GBSA, and PLIP studies confirmed the precise binding of 12c to the EGFR protein over 100 ns.

show abstract

Chemoselective N-alkylation of 2-hydroxycarbazole as a model for the synthesis of N-substituted pyrrole derivatives containing acidic functions

et al. 1995

View full text Add to dashboard Cite

Hydroxyindoles, Indole Alcohols, and Indolethiols

Cited by 6 publications

References 639 publications

Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR

Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR

New thieno[2,3‐d]pyrimidine derivatives as EGFR^WT and EGFR^T790M inhibitors: Design, synthesis, antiproliferative activities, docking studies, ADMET, toxicity, MD simulation studies

Chemoselective N-alkylation of 2-hydroxycarbazole as a model for the synthesis of N-substituted pyrrole derivatives containing acidic functions

Contact Info

Product

Resources

About

Hydroxyindoles, Indole Alcohols, and Indolethiols

Cited by 6 publications

References 639 publications

Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR

Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR

New thieno[2,3‐d]pyrimidine derivatives as EGFRWT and EGFRT790M inhibitors: Design, synthesis, antiproliferative activities, docking studies, ADMET, toxicity, MD simulation studies

Chemoselective N-alkylation of 2-hydroxycarbazole as a model for the synthesis of N-substituted pyrrole derivatives containing acidic functions

Contact Info

Product

Resources

About

New thieno[2,3‐d]pyrimidine derivatives as EGFR^WT and EGFR^T790M inhibitors: Design, synthesis, antiproliferative activities, docking studies, ADMET, toxicity, MD simulation studies