14316-16-6Relevant articles and documents
Design, synthesis, in vitro antiproliferative evaluation, and kinase inhibitory effects of a new series of imidazo[2,1- b ]thiazole derivatives
Abdel-Maksoud, Mohammed S.,Kim, Mi-Ryeong,El-Gamal, Mohammed I.,Gamal El-Din, Mahmoud M.,Tae, Jinsung,Choi, Hong Seok,Lee, Kyung-Tae,Yoo, Kyung Ho,Oh, Chang-Hyun
, p. 453 - 463 (2015)
Design and synthesis of a new series of 5,6-diarylimidazo[2,1-b]thiazole derivatives possessing terminal aryl sulfonamide moiety are described. Their in vitro antiproliferative activities against a panel of 57 human cancer cell lines of nine different cancer types were tested at the NCI. Compounds 8a, 8b, 8n, 8q, 8t, and 8u showed the highest mean % inhibition values over the 57 cell line panel at 10 1/4M, and they were further tested in 5-dose testing mode to determine their IC50 values. Among the six compounds, compound 8u possessing terminal para-hydroxybenzenesulfonamido moiety and ethylene linker showed the highest potency. It demonstrated superior potency than Sorafenib against eight different cell lines, and was equipotent to Sorafenib against COLO 205 colon cancer cell line. Its IC50 values over NCI-H460 non-small cell lung cancer cell line and MCF7 breast cancer cell line were 0.845 1/4M and 0.476 1/4M, respectively. Compounds 8a, 8b, 8q, 8t, and 8u showed high selectivity indices towards cancer cells over L132 normal lung cell line. Compound 8u showed potential inhibitory effects over the components of ERK pathway. Its IC50 value over V600E-B-RAF and C-RAF kinases were 39.9 nM and 19.0 nM, respectively.
Structural optimization of imidazothiazole derivatives affords a new promising series as B-Raf V600E inhibitors; synthesis, in vitro assay and in silico screening
Abdel-Maksoud, Mohammed S.,Ali, Eslam M. H.,Ammar, Usama M.,Ho Yoo, Kyung,Mersal, Karim I.,Oh, Chang-Hyun
, (2020)
BRAF mutation is commonly known in a number of human cancer types. It is counted as a potential component in treating cancer. In this study, based on structural optimization of previously reported inhibitors (3-fluro substituted derivatives of imidazo[2,1-b]thiazole-based scaffold), we designed and synthesized sixteen new imidazo[2,1-b]thiazole derivatives with m-nitrophenyl group at position 6. The electron withdrawing properties was reserved while the polarity was modified compared to previously synthesized compounds (-F). Furthermore, the new substituted group (–NO2) provided an additional H-bond acceptor(s) which may bind with the target enzyme through additional interaction(s). In vitro cytotoxicity evaluation was performed against human cancer cell line (A375). In addition, in vitro enzyme assay was performed against mutated B-Raf (B-Raf V600E). Compounds 13a, 13g and 13f showed highest activity on mutated B-Raf with IC50 0.021, 0.035 and 0.020 μM. All target compounds were tested for in vitro cytotoxicity against NCI 60 cell lines. Compounds 13a and 13g were selected for 5 doses test mode. Moreover, in silico molecular simulation was explored in order to explore the possible interactions between the designed compounds and the B-Raf V600E active site.
An epidermal growth factor receptor-targeted and endoplasmic reticulum-localized organic photosensitizer toward photodynamic anticancer therapy
Zhao, Xuan,Ma, Haixia,Chen, Juanjuan,Zhang, Fengling,Jia, Xiao,Xue, Jinping
, (2019)
The endoplasmic reticulum (ER), as the largest organelle in eukaryotic cells, plays complex but pivotal roles in multiple intracellular metabolic functions, including biosynthesis, sensing, and signal transduction, especially in proteins folding and post-translation modification. The ER is regarded as a promising target for anticancer therapy. Based on previous tumor-targeted photodynamic therapy (PDT), we chemically modified the phthalocyanine-based photosensitizer molecule with the small molecular anticancer-targeting drug erlotinib and the ER-targetable moiety methyl sulfonamide to develop an advanced photosensitizer EB-ER-Pc that can specifically target the subcellular organelle ER of EGFR-overexpressing cancer cells. The in vitro experiments show that the dual-target photosensitizer EB-ER-Pc can generate ROS in situ in the ER of the tumor target region to induce ER stress, upregulate Ca2+ ion level, and decrease mitochondrial membrane potential (MMP) to mediate cancer cells death and ablation. The results suggest that EB-ER-Pc is a promising candidate for effective photodynamic cancer therapy.
An endoplasmic reticulum targetable turn-on fluorescence probe for imaging application of carbon monoxide in living cells
Kong, Xiuqi,Lin, Weiying,Tang, Yonghe,Zhang, Yunyan
, (2021)
Carbon monoxide (CO) is a significant mediator in regulating endoplasmic reticulum (ER) stress, and its level may play a potential role in the treatment of vascular diseases combined with ER stress. In-situ visualization of CO in the ER helps to elucidate
Double-photon fluorescence probe for positioning formaldehyde response of endoplasmic reticulum and preparation method and application thereof
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Paragraph 0048; 0054; 0056; 0060; 0062; 0065; 0067; 0070..., (2021/11/06)
The invention discloses a double-photon fluorescence probe for positioning formaldehyde response in an endoplasmic reticulum and a preparation method and application thereof, and belongs to the technical field of analytical chemistry. The structural formu
Investigation of thiolysis of 4-substituted SBD derivatives and rational design of a GSH-selective fluorescent probe
Ji, Xiuru,Li, Shan,Sun, Lu,Tu, Xiaoqiang,Xi, Zhen,Yang, Chao,Ye, Haishun,Yi, Long
supporting information, p. 6527 - 6533 (2021/08/03)
In order to evaluate 7-sulfonamide benzoxadiazole (SBD) derivatives for the development of fluorescent probes, herein we investigated the thiolysis reactivity and selectivity of a series of SBD compounds with different atoms (N/O/S/Se) at the 4-position.