作者: Lou, Jian-Feng ; Jin, Cheng-Yun ; Shi, Lei ; Jian-Song ; Zhang, Yan-Bing ; Liu, Hong-Min ; Zhu, Ting ; Li, Dong ; Gao, Qiu-Lei ; Wu, Bo-Wen ; Zhang, Sai-Yang

With the expectation to find out new anti-gastric cancer agents with high efficacy and selectivity, a series of novel tertiary sulfonamide derivatives were synthesized and the anti-cancer activity was studied in three selected cancer cell lines (MGC-803, PC-3, MCF-7) in vitro. Some of the synthesized compounds could significantly inhibit the proliferation of these tested cancer cells and were more potent than the positive control (5-Fu). The structure-activity relationship of tertiary sulfonamide derivatives was explored in this report. Among the tested compounds, compound 13g containing benzimidazole moiety showed the best anti-proliferation activities against MGC-803 cells (IC₅₀ = 1.02 μM), HGC-27 cells (IC₅₀ = 1.61 μM), SGC-7901 (IC₅₀ = 2.30 μM) cells as well as the good selectivity between the cancer and normal cells. Cellular mechanism studies elucidated compound 13g inhibited the colony formation of gastric cancer cell lines. Meanwhile, compound 13g arrested cell cycle at G2/M phase and induced cell apoptosis. Mechanistically, compound 13g markedly decreased p-Akt and p-c-Raf expression, which revealed that compound 13g targeted gastric cancer cell lines via interfering with AKT/mTOR and RAS/Raf/MEK/ERK pathways. All the findings suggest that compound 13g might be a valuable lead compound for the anti-gastric cancer agents.

2014-11-01·Bioorganic & Medicinal Chemistry3区 · 医学

Synthesis of chiral chloroquine and its analogues as antimalarial agents

3区 · 医学

Article

作者: Srivastava, Kumkum ; Katti, Seturam B ; Agarwal, Pooja ; Soni, Awakash ; Dola, Vasanth R ; Sinha, Manish ; Haq, Wahajul ; Puri, Sunil K

In this investigation, we describe a new approach to chiral synthesis of chloroquine and its analogues. All tested compounds displayed potent activity against chloroquine sensitive as well as chloroquine resistant strains of Plasmodium falciparum in vitro and Plasmodium yoelii in vivo. Compounds S-13 b, S-13c, S-13 d and S-13 i displayed excellent in vitro antimalarial activity with an IC50 value of 56.82, 60.41, 21.82 and 7.94 nM, respectively, in the case of resistant strain. Furthermore, compounds S-13a, S-13c and S-13 d showed in vivo suppression of 100% parasitaemia on day 4 in the mouse model against Plasmodium yoelii when administered orally. These results underscore the application of synthetic methodology and need for further lead optimization.

2010-08-01·Bioorganic & Medicinal Chemistry3区 · 医学

Synthesis and biological evaluation of tetracyclic fluoroquinolones as antibacterial and anticancer agents

3区 · 医学

Article

作者: Salah A. Al-Trawneh ; Paola Vicini ; Mustafa M. El-Abadelah ; Andrea Cavazzoni ; Jalal A. Zahra ; Pier G. Petronini ; Marwan R. Kamal ; Matteo Incerti ; Roberta R. Alfieri ; Franca Zani

A simple and efficient synthesis of 6-fluoro-4-oxopyrido[2,3-a]carbazole-3-carboxylic acids (13a-e) and a structurally related 6-fluoro-4-oxothieno[2',3':4,5]pyrrolo[3,2-h]quinoline (13f) was achieved via Stille arylation of 7-chloro-6-fluoro-8-nitro-4-oxoquinoline-3-carboxylate and a subsequent microwave-assisted phosphite-mediated Cadogan reaction. The new compounds were tested for their in vitro antimicrobial and antiproliferative activity. The ability of 13a-f to inhibit the activity of DNA gyrase and topoisomerase IV was also investigated. The thieno isostere (13f) emerged as the most active antibacterial, while the 9-fluoro derivative (13e) was the most potent against multidrug-resistant staphylococci. Compounds 13a, 13c-f displayed growth inhibition against MCF-7 breast tumor and A549 non-small cell lung cancer cells coupled with an absence of cytotoxicity toward normal human-derm fibroblasts (HuDe). Compound 13e was the most active anticancer against MCF-7 cells, with greater potency than ellipticine (IC(50) 0.8 and 1.6muM, respectively). The most active compounds in this series show promise as dual acting anticancer and antibacterial chemotherapeutics.

100 项与 Compound 13a (温州医科大学) 相关的药物交易

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