Antiproliferative Agents That Interfere with the Cell Cycle at the G₁→S Transition: Further Development and Characterization of a Small Library of Stilbene‐Derived Compounds

Abstract

In this continuation of our research on derivatives containing the stilbene privileged structure or that are derived from it, we report the results of further studies carried out on the previously initiated collection of compounds. We used a parallel synthetic approach to rapidly obtain small sets of compounds and started the annotation of the library in progress by calculating some physicochemical properties to be eventually correlated with biological activities. A pharmacophore for the antiproliferative activity was also built to summarize the features of the library. We evaluated the antiproliferative and pro-apoptotic activities of all compounds as well as the cell-cycle effects of some representative compounds. After in-depth investigations, 3'-phenyl-[1,1';4',1'']terphenyl-4,3'',5''-triol showed the most interesting biological profile, as it interferes with cell-cycle progression at the G(1)-->S transition, acting on retinoblastoma phosphorylation and inducing cell differentiation.

Synthesis of Diiodinated Biphenyls and Iodinated meta‐Terphenyls by Regioselective Suzuki–Miyaura Cross‐Coupling Reactions of 5‐Substituted 1,2,3‐Triiodobenzenes

“…Biphenyl derivative 1 is also useful for the treatment or prophylaxis of diseases that are associated with bone disorders, such as osteoporosis, or with the excessive secretion of the parathyroid hormone (PTH), such as hyperparathyroidism 1. Additionally, 5‐bromo‐2‐iodo‐1,1′‐biphenyl ( 2 ), a small iodinated biphenyl pharmacophore, is reported to have antiproliferative activity that interferes with cell‐cycle progression at the G1→S transition by acting on retinoblastoma phosphorylation and inducing cell differentiation 2. Furthermore, methyl 3′‐fluoro‐6‐iodo‐5′‐(trifluoromethyl)‐[1,1′‐biphenyl]‐3‐carboxylate ( 3 ), which is a biaryl ester derivative that contains an iodo group at the C‐6 atom of the aromatic ring, was found to be a platelet‐activating factor receptors antagonist 3…”

Antiparasitic effect of stilbene and terphenyl compounds againstTrypanosoma cruziparasites

“…Compounds ST18 and 6 were synthesized as reported by Kim et al [12]; compounds 1-5 and 8-10 were prepared as previously described by us [6], compounds 7, TR4 and 13-14 were prepared as previously described by us [7], 15 was synthesized as reported by Pizzirani et al [5]. The purity of compound was determined by elemental analyses and was ≥ 97%.…”

“…Many drugs available in the market are natural products as found in nature or compounds designed based on the structure and activity of these natural products (semi-synthetic or completely synthetic) [4]. Recently, several natural and synthetic stilbene and terphenyl have been studied for their anticancer and leishmanicidal properties [5][6][7][8], in particular we evaluated the antileishmanial activity of two compounds, a trans-stilbene derivatives and a terphenyl derivatives, namely trans-1,3-dimethoxy-5-(4-methoxystyryl) benzene (ST18) and 3,4'',5trimethoxy-1,1':2',1''-terphenyl (TR4), presented the best activity and safety profiles [9,10].…”

Identification of a 2,4-diaminopyrimidine scaffold targeting Trypanosoma brucei pteridine reductase 1 from the LIBRA compound library screening campaign

“…antitrypanosomal activity [40] and oncology [41]) and donated to the Italian Institute of Technology (IIT) by several Italian academic research groups. Additional details regarding the main contributors and providers of the compounds forming the LIBRA library are reported in Supporting Information.…”