A synthetic 2,3-diarylindole induces microtubule destabilization and G2/M cell cycle arrest in lung cancer cells

Thanaussavadate, Bongkotrat; Ngiwsara, Lukana; Lirdprapamongkol, Kriengsak; Svasti, Jisnuson; Chuawong, Pitak

doi:10.1016/j.bmcl.2019.126777

Cited by 12 publications

(18 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tubulin polymerization inhibitors have been previously reported to disrupt cell mitosis and induce cell cycle arrest . Thus, flow cytometry analysis was performed to examine the effects of compound 12b on the cell cycle of MCF-7 cells.…”

Section: Results and Discussionmentioning

confidence: 99%

Discovery of Novel Benzimidazole and Indazole Analogues as Tubulin Polymerization Inhibitors with Potent Anticancer Activities

Ren

Wang

et al. 2021

J. Med. Chem.

View full text Add to dashboard Cite

Novel indazole and benzimidazole analogues were designed and synthesized as tubulin inhibitors with potent antiproliferative activities. Among them, compound 12b exhibited the strongest inhibitory effects on the growth of cancer cells with an average IC50 value of 50 nM, slightly better than colchicine. 12b exhibited nearly equal potency against both, a paclitaxel-resistant cancer cell line (A2780/T, IC50 = 9.7 nM) and the corresponding parental cell line (A2780S, IC50 = 6.2 nM), thus effectively overcoming paclitaxel resistance in vitro. The crystal structure of 12b in complex with tubulin was solved to 2.45 Å resolution by X-ray crystallography, and its direct binding was confirmed to the colchicine site. Furthermore, 12b displayed significant in vivo antitumor efficacy in a melanoma tumor model with tumor growth inhibition rates of 78.70% (15 mg/kg) and 84.32% (30 mg/kg). Collectively, this work shows that 12b is a promising lead compound deserving further investigation as a potential anticancer agent.

show abstract

Section: Results and Discussionmentioning

confidence: 99%

Discovery of Novel Benzimidazole and Indazole Analogues as Tubulin Polymerization Inhibitors with Potent Anticancer Activities

Ren

Wang

et al. 2021

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…This method blocks cells in the G2/M‐phase and is useful to synchronize or to treat cancer cells. [ 40–42 ] However, these drugs induce various abnormalities in cells (return to interphase, multiple mitotic spindle formation, or apoptosis activation), according to the duration of treatment and the cell type. [ 22,26,43 ] Nevertheless, this method is simple, low cost, and induces a high degree of synchronization.…”

Section: Discussionmentioning

confidence: 99%

Cell Cycle Synchronization of the Murine EO771 Cell Line Using Double Thymidine Block Treatment

et al. 2020

View full text Add to dashboard Cite

This study shows that double thymidine block treatment efficiently arrests the EO771 cells in the S‐phase without altering cell growth or survival. A long‐term analysis of cell behavior, using 5(6)‐carboxyfluorescein diacetate N‐succinimidyl ester (CFSE) staining, show synchronization to be stable and consistent over time. The EO771 cell line is a medullary breast‐adenocarcinoma cell line isolated from a spontaneous murine mammary tumor, and can be used to generate murine tumor implantation models. Different biological (serum or amino acid deprivation), physical (elutriation, mitotic shake‐off), or chemical (colchicine, nocodazole, thymidine) treatments are widely used for cell synchronization. Of the different methods tested, the double thymidine block is the most efficient for synchronization of murine EO771 cells if a large quantity of highly synchronized cells is recommended to study functional and biochemical events occurring in specific points of cell cycle progression.

show abstract

“…In addition, 2, 3-diarylindole derivatives have been reported as inhibitors of tubulin polymerization [45]. Thanaussavadate et al [46,47] designed and synthesized a FITC fluorophore via a hydrophilic linker to 2,3-diarylindole derivatives 19a-19d (Figure 9A) and studied their biological activity against non-small cell lung cancer cell lines. Through Kazan et al [44] synthesized a class of indole-2-carbohydrazides (17a-17e and 18a-18h) as potent tubulin polymerization inhibitors, and evaluated their anti-proliferative activity.…”

Section: Aroyindolesmentioning

confidence: 99%

“…Meanwhile, compound In addition, 2, 3-diarylindole derivatives have been reported as inhibitors of tubulin polymerization [45]. Thanaussavadate et al [46,47] designed and synthesized a FITC fluorophore via a hydrophilic linker to 2,3-diarylindole derivatives 19a-19d (Figure 9A) and studied their biological activity against non-small cell lung cancer cell lines. Through the structure-activity relationship study, the optimal position of the linker was determined to obtain the compound 20 with the most excellent inhibitory activity against A549 cells (IC 50 = 5.17 ± 1.61 µM) and could inhibit the polymerization of tubulin in vitro.…”

Section: Fused Indolementioning

confidence: 99%

Indole-Based Tubulin Inhibitors: Binding Modes and SARs Investigations

et al. 2022

View full text Add to dashboard Cite

Tubulin inhibitors can interfere with normal cell mitosis and inhibit cell proliferation through interfering with the normal structure and function of microtubules, forming spindle filaments. Indole, as a privileged pharmacological skeleton, has been widely used in anti-cancer inhibitors. A variety of alkaloids containing an indole core obtained from natural sources have been proven to inhibit tubulin polymerization, and an ever-increasing number of synthetic indole-based tubulin inhibitors have been reported. Among these, several kinds of indole-based derivatives, such as TMP analogues, aroylindoles, arylthioindoles, fused indole, carbazoles, azacarbolines, alkaloid nortopsentin analogues and bis-indole derivatives, have shown good inhibition activities towards tubulin polymerization. The binding modes and SARs investigations of synthetic indole derivatives, along with a brief mechanism on their anti-tubulin activity, are presented in this review.

show abstract

A synthetic 2,3-diarylindole induces microtubule destabilization and G2/M cell cycle arrest in lung cancer cells

Cited by 12 publications

References 25 publications

Discovery of Novel Benzimidazole and Indazole Analogues as Tubulin Polymerization Inhibitors with Potent Anticancer Activities

Discovery of Novel Benzimidazole and Indazole Analogues as Tubulin Polymerization Inhibitors with Potent Anticancer Activities

Cell Cycle Synchronization of the Murine EO771 Cell Line Using Double Thymidine Block Treatment

Indole-Based Tubulin Inhibitors: Binding Modes and SARs Investigations

Contact Info

Product

Resources

About