Identification of new fisetin analogs as kinase inhibitors: Data on synthesis and anti-skin cancer activities evaluation

Abstract

This article contains supplemental datasets of the recently published related research article “Synthesis, Inverse Docking-Assisted Identification and in vitro Biological Characterization of Flavonol-based Analogs of Fisetin as c-Kit, CDK2 and mTOR Inhibitors against Melanoma and Non-melanoma Skin Cancers” by Roy et al., [1] . It provides in-depth data not included in the original co-submission on the biophysical, molecular docking, and biological characterization of newly synthesized flavonol-based analogs of fisetin, a natural dietary small molecule with anticancer and anti-inflammatory properties. These synthetic small molecules were investigated as new, potential single and/or multi-kinase inhibitors of the cyclin-dependent kinase-2 (CDK2), receptor tyrosine kinases (c-KITs), and mammalian targets of rapamycin (mTOR) targets, potentially active against melanoma or non-melanoma skin cancers. Furthermore, this data-in-brief article comprises additional sets of results on several aspects of the properties of the dual and multiple kinase inhibitor compounds’ effects that were not presented in the associated article, including the activated targets that are dysregulated in skin cancers; the effects on markers of apoptosis; on colony formation; and in scratch wound healing assays. The study has identified a panel of novel fisetin analogs that are either single- or multi-kinase inhibitors, which may be further developed as active for the treatment of melanoma and non-melanoma skin cancers. The dataset presented herein will be utilized for additional studies aiming to establish a biological platform to steer for predictive and experimental screening of novel flavonoids and analogs in relevant organoids, humanized animal models and in vivo disease models. The present results should also serve as a key stepping-stone towards enabling target-structure-based design, synthesis and initial testing of novel analogs or derivatives of fisetin. The current study may eventually lead to the development of safe, promising and preclinical candidate entities for treatment of skin and other forms of cancers as well as various other human diseases, which can possibly add to the general armamentarium of promising and safe drugs for health promotion.

Multifaceted approach toward mapping out the anticancer properties of small molecules via in vitro evaluation on melanoma and nonmelanoma skin cancer cells, and in silico target fishing

“…All statistical analyses were performed using GraphPad Prism Software version 9.1 (GraphPad Prism Inc.) (Roy et al, 2021a(Roy et al, , 2021b. All quantitative and grouped data are expressed and presented as means ± standard deviation (SD) or ±, standard error of the mean (SEM) from at least three independent experiments.…”

“…The scratch wound‐healing assay was performed to evaluate the ability of compound 11 or 13 to limit the migration and wound closure using a previously described protocol (Chamcheu, et al., 2019; Roy et al., 2021a, 2021b). Briefly, a 24‐well plate seeded with cells was incubated until a fully confluent monolayer of cells was attained.…”

“…This assay was performed to demonstrate the colony formation potential of the active compounds on SCC-12 and SK-MEL-28 cell lines, following a previously described protocol (Roy et al, 2021a(Roy et al, , 2021b. Briefly, 3000 viable cells treated with compounds 11 or 13 at varying concentrations (0, ½IC 50 , IC 50 , and 1½IC 50 ) for 48 h in a T-25 flask were harvested and seeded into a 10 cm 2 plate in quadruplicates in respective drug-free growth medium.…”

“…Control cells were treated with the vehicle (DMSO) at concentrations (0.01%-0.2%), not affecting cell viability. From these 10 mM stock solutions prepared in DMSO, escalating concentrations were prepared using the corresponding cell growth media as a diluent, and the cells (65%-75% confluent) were treated with (0-40 μM) or without the drug in sext-to octuplicate and incubated for 48 h. All treatment protocols and controls were prepared as previously described (Roy et al, 2021a(Roy et al, , 2021b.…”

“…The results from escalating concentration of each test and control (cisplatin) agent were analyzed using the zero drug control groups as the relative comparator and are expressed as a percentage following the equation: [(absorbance in treatment group/absorbance in control) × 100%]. GraphPad Prism software version 9.3 (GraphPad Software, Inc.) was then used to compute the various IC 50 values as earlier described (Roy et al, 2021a(Roy et al, , 2021b).…”