A Promising Anticancer Agent Dimethoxycurcumin: Aspects of Pharmacokinetics, Efficacy, Mechanism, and Nanoformulation for Drug Delivery

Abstract

Curcumin is a well-known anticancer natural product with various significant bioactivities that has been well documented, but its widespread use is mainly hindered by insufficient ADME properties such as poor solubility and low metabolic stability. Dimethoxycurcumin (DiMC) is a kind of lipophilic compound derived from curcumin that maintains its anticancer potency and has greatly improved systematic bioavailability. Therefore, DiMC is regarded as a promising plant-derived anticancer agent that deserves to be well developed. Herein, we concentrate on the published work by those from original research groups concerned with the pharmacokinetics, efficacy, and mechanism of DiMC involved in the treatment of various tumors, as well as the nanoformulations for effective drug delivery.

Complex polymeric nanomicelles co-delivering doxorubicin and dimethoxycurcumin for cancer chemotherapy

“…Herein the two drug molecules involved were DOX and DiMC, a chemotherapeutic agent for various malignancies that can cause cell necrosis and apoptosis by interacting with DNA intercalation and inhibiting RNA transcription, and a promising naturally derived multifunctional anti-cancer agent, respectively (Sohail et al., 2021a ; 2021b ). It is well-known that combination therapy using drugs with different mechanisms can be synergistic, additive or antagonistic in therapeutic effects, depending greatly on the compatibility ratio of drugs (Pritchard et al., 2013 ).…”

“…In contrast, the lipophilic DiMC could be entrapped into the inner hydrophobic core of the micelles through strong hydrophobic interaction during amphiphilic self-assembly. Meanwhile, the acidic hydroxyl group in DiMC from keto-enol tautomerism (Sohail et al., 2021a ; Jayakumar et al, 2016 ) could lead to efficient interaction with DOX via its basic amino group ( Figure 4C ). In view of this, DiMC could be regarded as a vital link that significantly improved the interactions among the copolymer and both drugs, therefore resulting in high encapsulation yields of CPM-DD, particularly a remarkable increase in the encapsulation efficiency of DOX.…”

“…Cancer is a kind of disease with the most remarkable fatality rate globally and the most challenging hurdle to overcome in aging humans (Bray et al., 2018 ). Chemotherapeutic agents clinically still play a significant role in eradicating tumor cells because of their efficacies, among which the anthracycline antibiotic doxorubicin (DOX) is a common component of multiple chemotherapy drug regimens used to treat various solid and hematological malignancies such as breast carcinoma, soft tissue sarcomas, osteosarcoma, leukemia and lymphomas (Moraes et al., 2021 ; Sohail et al., 2021a ; Waks & Winer 2019 ). There are several molecular targets involved in the cytotoxicity of DOX, and its substantial anti-cancer action could be ascribed to DNA intercalation and generation of ROS and centered-carbon radicals (Tacar et al., 2012 ; Gonçalves et al., 2020 ).…”

Dimethoxycurcumin Acidifies Endolysosomes and Inhibits SARS-CoV-2 Entry

“…As a methylated analog of curcumin (13,15), dimethoxycurcumin (DiMC) is more metabolically stable, has better bioavailability, and exerts greater antioxidant (16) and anti-inflammatory properties (17) than does curcumin. Here, we determined effects of DiMC on the entry of SARS-CoV-2 pseudo-virus and found that DiMC blocked the entry of SARS-CoV-2 pseudo-virus in Calu-3 human non-small cell lung adenocarcinoma cells and Vero E6 green monkey kidney epithelial cells, acidified lysosomes, enhanced lysosome degradation capabilities, and promoted lysosome degradation of ACE2 as well as pseudo-SARS-CoV-2 and the SARS-CoV-2 S1 protein.…”

A Ca-based nano bio-coordination polymer providing reversible structural conversion with ability to enhance cytotoxicity of curcumin and induce apoptosis in human gastric cancer AGS cells

“…3 However, there are some obstacles to the clinical application of curcumin, such as its low water solubility (about 11 ng mL −1 ), poor absorption, and instability. 4,5 Preclinical and clinical studies indicate the poor absorption of CCM following oral administration. Therefore, finding a method to solve this problem could be helpful in the future progress of cancer treatments through oral administration.…”