Discovery of novel N-benzylarylamide-dithiocarbamate based derivatives as dual inhibitors of tubulin polymerization and LSD1 that inhibit gastric cancers

Novel Acrylate-Based Derivatives: Design, Synthesis, Antiproliferative Screening, and Docking Study as Potential Combretastatin Analogues

“…Previous reports suggested that β-tubulin polymerization is a multistep process triggered by the creation of assembled protofilaments as well as the regulation of actin filaments . As a crucial component of the cytoskeleton, β-tubulin polymerization has been identified as a possible target in cancer drug development . To evaluate whether the representative active acrylate derivatives target the tubulin-microtubule system, compounds 4b , 5a, and 5e were selected to investigate their abilities to disrupt microtubule assembly.…”

“… 35 As a crucial component of the cytoskeleton, β-tubulin polymerization has been identified as a possible target in cancer drug development. 36 To evaluate whether the representative active acrylate derivatives target the tubulin-microtubule system, compounds 4b , 5a, and 5e were selected to investigate their abilities to disrupt microtubule assembly. The impact of selected newly prepared acrylate derivatives 4b , 5a, and 5e on β-tubulin polymerization at a concentration value of 25 μM is outlined in Figure 2 .…”

Combination Therapy and Dual-Target Inhibitors Based on LSD1: New Emerging Tools in Cancer Therapy

“…Recently, two dual-target LSD1/HDACs inhibitors, 4SC-202 and JBI-802, have entered clinical trials to evaluate their efficacy, safety, and tolerability, proving the feasibility of multitarget drugs based on LSD1. The multitarget inhibitors related to LSD1 and their design strategies in recent years are also reviewed, − while most of them exhibited moderate enzyme inhibitory activity and are still faced with common challenges, such as toxicity, PK, and PD after entering clinical trials. In addition, Groves et al discovered that LSD1 degrader UM171 and HDAC inhibitors exhibit a synergistic inhibitory effect on DIPGs cells, indicating the scope of multitarget drugs extends beyond inhibitors.…”

“…9). 150 Among these derivatives, MY-943 (Table 3, Figure 9) showed noteworthy spectral inhibitory effects on cancer cells, particularly GC cells MGC-803 and SGC-7901. Additionally, it demonstrated a dual inhibitory impact on the polymerization of tubulin (IC 50 = 3.1 μM) and LSD1 (IC 50 = 2.8 μM).…”

“…Recently, Yuan et al employed the molecular hybridization principle to design and synthesize N -benzoylamide dithiocarbamate derivatives by connecting the N -benzoylamide fragment of compound 15 (colchicine binding site inhibitor) with the dithiocarbamate piperazine fragment of compound 13 (Figure ). Among these derivatives, MY-943 (Table , Figure ) showed noteworthy spectral inhibitory effects on cancer cells, particularly GC cells MGC-803 and SGC-7901. Additionally, it demonstrated a dual inhibitory impact on the polymerization of tubulin (IC 50 = 3.1 μM) and LSD1 (IC 50 = 2.8 μM).…”