Bioactivities and Mechanisms of Action of Diphyllin and Its Derivatives: A Comprehensive Systematic Review

Abstract

Natural products are treasure houses for modern drug discovery. Diphyllin is a natural arylnaphthalene lignan lactone isolated from the leaf of Astilboides tabularis. Studies have found that it possesses plenty of bioactivity characteristics. In this paper, we reviewed the structure, bioactivity, and mechanism of action of diphyllin and its derivatives. The references were obtained from PubMed, Web of Science, and Science Direct databases up to August 2023. Papers without a bio-evaluation were excluded. Diphyllin and its derivatives have demonstrated V-ATPase inhibition, anti-tumor, anti-virus, anti-biofilm, anti-inflammatory, and anti-oxidant activities. The most studied activities of diphyllin and its derivatives are V-ATPase inhibition, anti-tumor activities, and anti-virus activities. Furthermore, V-ATPase inhibition activity is the mechanism of many bioactivities, including anti-tumor, anti-virus, and anti-inflammatory activities. We also found that the galactosylated modification of diphyllin is a common phenomenon in plants, and therefore, galactosylated modification is applied by researchers in the laboratory to obtain more excellent diphyllin derivatives. This review will provide useful information for the development of diphyllin-based anti-tumor and anti-virus compounds.

New highly selective antivirals for Chikungunya Virus identified from the screening of a drug-like compound library

“…Diphyllin, is an arylnaphthalene lignan lactone that can be isolated from many traditional medicinal plants. It has multiple bioactivities reported such as antitumor, anti-inflammatory, and antimicrobial activities (reviewed in [30]) and was found to inhibit the replication of many fungal, bacterial, and protozoan pathogens (reviewed in [31]). Diphyllin was originally reported to decrease vacuolar (H+)ATPase (or V-ATPase) activity and to neutralize the pH of lysosomes at nanomolar concentrations [31, 32].…”

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review

“…Wei et al completed the synthesis and antitumor evaluation of SIN derivatives modified at the C-1, 4, 7, and 8 positions of SIN. They identified derivatives 2d (5) and 6b (6) with inhibition rates of 79.72% and 84.54% against MDA-MB-231 and A172 cells, respectively, at 10 µg/mL. The inhibition rate of compound 2c was 80.49% against A549 at 8.8 µM, displaying superior antitumor activity compared to the positive control 5-FU [63].…”

“…Despite their significance, NPs often present challenges, such as low activity or ambiguous mechanisms of action [ 4 ]. Consequently, modifying NPs to enhance activities and elucidate targets or mechanisms of action is of paramount importance [ 5 , 6 ]. Sinomenine (SIN, 1 ), an isoquinoline alkaloid, is isolated from the roots and stems of Sinomenium acutum or Caulis Sinomenii .…”