Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Discovery of Polyoxypregnane Derivatives From Aspidopterys obcordata With Their Potential Antitumor Activity.

ABSTRACT: The bioassay-guided phytochemical study of an ethnic medicinal plant Aspidopterys obcorda ta Hemsl. var. obcordata results in the isolation of eight new polyoxypregnane derivatives, named aspidatasides A-H (1-8), along with ten known analogs (9-18). The series polyoxypregnane derivatives were screened for their cytoxic activity against HL-60 cells, and compound 2 showed the highest potency with an IC₅₀ 8.03 μM. Preliminary structure-activity relationship studies displayed that the sugar chain and double bond could notably impact their biological activity.

SUBMITTER: Guo HW

PROVIDER: S-EPMC8766633 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Discovery of Polyoxypregnane Derivatives From Aspidopterys obcordata With Their Potential Antitumor Activity.

Guo Hong-Wei HW Tian Yun-Gang YG Liu Yi-Han YH Huang Jia J Wang Jian-Xia JX Long Hua H Wei Hua H

Frontiers in chemistry 20220105

The bioassay-guided phytochemical study of an ethnic medicinal plant Aspidopterys obcorda ta Hemsl. var. obcordata results in the isolation of eight new polyoxypregnane derivatives, named aspidatasides A-H (1-8), along with ten known analogs (9-18). The series polyoxypregnane derivatives were screened for their cytoxic activity against HL-60 cells, and compound 2 showed the highest potency with an IC50 8.03 μM. Preliminary structure-activity relationship studies displayed that ...[more]

PMID: 35071186

Similar Datasets

Five New Polyoxypregnane Glycosides from the Vines of Aspidopterysobcordata and Their Antinephrolithiasis Activity.

Project description:From the dried vines of Aspidopterys obcordata Hemsl, five new polyoxypregnane glycosides, named obcordatas J-N (1-5), were obtained. Their structures were fully elucidated and characterized by HRESIMS and extensive spectroscopic data. In addition, all of the new compounds were screened for their antinephrolithiasis activity in vitro. The results showed that compounds 1-3 have prominent protective effects on calcium oxalate crystal-induced human kidney 2 (HK-2) cells, with EC50 values ranging from 6.72 to 14.00 μM, which is consistent with the application value of A. obcordata in folk medicine for kidney stones.

| S-EPMC9324186 | biostudies-literature

Discovery of Novel Pyrido-pyridazinone Derivatives as FER Tyrosine Kinase Inhibitors with Antitumor Activity.

Project description:To obtain a new anticancer drug, we focused on FER tyrosine kinase. Starting with high-throughput screening with our in-house chemical library, compound 1, which has a pyridine moiety, was found. Referring to their X-ray crystal structure with FES proto-oncogene tyrosine kinase, as a surrogate of FER followed by chemical modification including scaffold hopping of the pyridine template, we discovered pyrido-pyridazinone derivatives with potent FER kinase inhibitory activity. Here, we disclose the structure-activity relationship on the scaffold and representative compound 21 (DS21360717), which showed in vivo antitumor efficacy in a subcutaneous tumor model.

| S-EPMC6511961 | biostudies-literature

Discovery of Novel Quinazoline Derivatives as Potent Antitumor Agents.

Project description:In this work, we designed and synthesized a novel series of quinazoline derivatives 6-19 and then evaluated their broad-spectrum antitumor activity against MGC-803, MCF-7, PC-9, A549, and H1975, respectively. Most of them demonstrated low micromolar cytotoxicity towards five tested cell lines. In particular, compound 18 exhibited nanomolar level inhibitory activity against MGC-803 cells with an IC50 value of 0.85 μM, indicating approximately a 32-fold selectivity against GES-1 (IC50 = 26.75 μM). Further preclinical evaluation showed that compound 18 remarkably inhibited the migration of MGC-803 cells, induced cell cycle arrest at G2/M, and induced MGC-803 apoptosis, resulting in decreasing the expression of both Bcl-2 and Mcl-1, and up-regulating the expression of both Bax and cleaved PARP. No death or obvious pathological damage was observed in mice by acute toxicity assay. The in vivo antitumor evaluation suggested that compound 18 significantly decreased the average tumor volume and tumor weight without any effect on body weight, which is better than 5-Fu. Therefore, compound 18 can be used as a lead compound for the further development of antitumor drugs in the future.

| S-EPMC9230651 | biostudies-literature

Antitumor activity of bis-indole derivatives.

Project description:This paper reports the synthesis of compounds formed by two indole systems separated by a heterocycle (pyridine or piperazine). As a primary screening, the new compounds were submitted to the National Cancer Institute for evaluation of antitumor activity in the human cell line screen. The pyridine derivatives were far more active than the piperazine derivatives. For the study of the mechanism of action, the most active compounds were subjected to COMPARE analysis and to further biological tests including proteasome inhibition and inhibition of plasma membrane electron transport. The compound bearing the 5-methoxy-2-indolinone moiety was subjected to the first in vivo experiment (hollow fiber assay) and was active. It was therefore selected for the second in vivo experiment (human tumor xenograft in mice). In conclusion we demonstrated that this approach was successful, since some of the compounds described are much more active than the numerous, so far prepared and tested 3-indolylmethylene-2-indolinones.

| S-EPMC2754042 | biostudies-literature

Antitumor Activity of New Olivacine Derivatives.

Project description:Olivacine is an alkaloid-containing pyridocarbazole structure. It is isolated from the bark of the evergreen timber tree, Aspidosperma olivaceum. Its well-documented anticancer activity led to the synthesis of new derivatives, which are semisynthetic and fully synthetic pyridocarbazoles. This study aimed to evaluate the potential antineoplastic activity of four newly synthesized olivacine derivatives. Multidrug resistance is a common phenomenon causing failure in the chemotherapy of many tumors. It is mainly related to increased function of P-glycoprotein, an efflux pump removing cytostatic out of the cells. The cell lines used in the study were colorectal carcinoma cell lines: LoVo (doxorubicin-sensitive) and LoVo/DX (doxorubicin-resistant). The NHDF cell line was used to assess cell viability. First, the cells were incubated with olivacine derivatives. In the next step, the following assays were performed: DCF-DA assay, MTT assay, rhodamine 123 assay, detection of apoptosis, proliferation inhibition-mitotic index. The tested compounds showed higher antineoplastic potential and lower toxicity than the reference compound ellipticine. The results indicate that the new olivacine derivatives are good candidates for future anticancer drugs.

| S-EPMC7321363 | biostudies-literature

Discovery of Phenylpyrazole Derivatives as a New Class of Selective Inhibitors of MCL-1 with Antitumor Activity

Project description: Not available

| S-EPMC11209699 | biostudies-literature

Synthesis and Discovery of Ligustrazine-Heterocycle Derivatives as Antitumor Agents.

Project description:Ligustrazine (TMP) is a natural pyrazine alkaloid extracted from the roots of Ligusticum Chuanxiong Hort, which has the potential as an antitumor agent. A series of 33 ligustrazine-heterocycle (TMPH) derivatives were designed, synthesized, and investigated via antitumor screening assays, molecular docking analysis, and prediction of drug-like properties. TMP was attached to other heterocyclic derivatives by an 8-12 methylene alkyl chain as a linker to obtain 33 TMPH derivatives. The structures were confirmed by 1H-NMR, 13C-NMR, and high-resolution mass spectroscopy spectral (HR-MS) data. The antiproliferative activity against human breast cancer MCF-7, MDA-MB-231, mouse breast cancer 4T1, mouse fibroblast L929, and human umbilical vein endothelial HUVEC cell lines was evaluated by MTT assay. Compound 12-9 displayed significant inhibitory activity with IC50 values in the low micromolar range (0.84 ± 0.02 µM against the MDA-MB-231 cell line). The antitumor effects of compound 12-9 were further evaluated by plate cloning, Hoechst 33 342 staining, and annexin V-FITC/PI staining. The results indicated that compound 12-9 inhibited the proliferation and apoptosis of breast cancer cells. Furthermore, molecular docking of compound 12-9 into the active site of the Bcl-2, CASP-3, and PSMB5 target proteins was performed to explore the probable binding mode. The 33 newly synthesized compounds were predicted to have good drug-like properties in a theoretical study. Overall, these results indicated that compound 12-9 inhibited cell proliferation through PSMB5 and apoptosis through Bcl-2/CASP-3 apoptotic signaling pathways and had good drug-like properties. These results provided more information, and key precursor lead derivatives, in the search for effective bioactive components from Chinese natural medicines.

| S-EPMC9358002 | biostudies-literature

Synthesis, biological evaluation and computer-aided discovery of new thiazolidine-2,4-dione derivatives as potential antitumor VEGFR-2 inhibitors.

Project description:In this study, novel VEGFR-2-targeting thiazolidine-2,4-dione derivatives with potential anticancer properties were designed and synthesized. The ability of the designed derivatives to inhibit VEGFR-2 and stop the growth of three different cancer cell types (HT-29, A-549, and HCT-116) was examined in vitro. The IC50 value of compound 15, 0.081 μM, demonstrated the best anti-VEGFR-2 potency. Additionally, compound 15 showed remarkable anti-proliferative activities against the tested cancer cell lines, with IC50 values ranging from 13.56 to 17.8 μM. Additional flow cytometric investigations showed that compound 15 increased apoptosis in HT-29 cancer cells (from 3.1% to 31.4%) arresting their growth in the S phase. Furthermore, compound 15's apoptosis induction in the same cell line was confirmed by increasing the levels of BAX (4.8-fold) and decreasing Bcl-2 (2.8-fold). Also, compound 15 noticeably increased caspase-8 and caspase-9 levels by 1.7 and 3.2-fold, respectively. Computational methods were used to perform molecular analysis of the VEGFR-2-15 complex. Molecular dynamics simulations and molecular docking were utilized to analyze the complex's kinetic and structural characteristics. Protein-ligand interaction profiler analysis (PLIP) determined the 3D interactions and binding conformation of the VEGFR-2-15 complex. DFT analyses also provided insights into the 3D geometry, reactivity, and electronic characteristics of compound 15. Computational ADMET and toxicity experiments were conducted to determine the potential of the synthesized compounds for therapeutic development. The study's findings suggest that compound 15 might be an effective anticancer lead compound and could guide future attempts to develop new drugs.

| S-EPMC10508263 | biostudies-literature

Design, Synthesis, and Antitumor Activity of Erlotinib Derivatives.

Project description:Nineteen erlotinib derivatives bearing different 1,2,3-triazole moieties were designed, synthesized, and evaluated for their potential against different cancer cell lines. The structures of the synthesized compounds were confirmed via 1H NMR, 13C NMR, and HR MS. Preliminary antitumor activity assay results suggested that some compounds showed remarkable inhibitory activity against different cancer cell lines including the corresponding drug-resistant ones. Among these compounds, 3d was the most promising one with an IC50 of 7.17 ± 0.73 μM (KYSE70TR), 7.91 ± 0.61 μM (KYSE410TR), 10.02 ± 0.75 μM (KYSE450TR), 5.76 ± 0.3 3 μM (H1650TR), and 2.38 ± 0.17 μM (HCC827GR). A preliminary mechanism study suggested that compound 3d suppressed cancer cell proliferation through the EGFR-TK pathway.

| S-EPMC9065260 | biostudies-literature

Clindamycin Derivatives: Unveiling New Prospects as Potential Antitumor Agents.

Project description:This study delves into the exploration of Clindamycin derivatives, specifically compounds 3 and 3e, to unveil their antitumor potential by employing a multidisciplinary approach. Screening a repertoire of 200 Clindamycin-associated targets pinpointed the Family A G-protein-coupled receptor as a prominent antitumor candidate. Subsequent analyses unearthed 16 pertinent antitumor proteins, with compound 3 exhibiting robust affinity towards a specific protein via stable hydrogen bonding. Molecular dynamics simulations underscored the adrenergic receptor β as a pivotal target, primarily situated in the plasma membrane and endoplasmic reticulum. These revelations hint towards compound 3's potential to bolster natural defense mechanisms against tumors by modulating immune responses within the tumor microenvironment, thus paving the way for novel avenues in antitumor drug development. Furthermore, employing the MTT assay, we evaluated the anti-HepG2 cell activity of compounds 3 and 3e, with 5-fluorouracil serving as the control drug. Results revealed that compound 3 exhibited significant differences (p < 0.01) across all concentrations (2.5, 5, 10 μg/mL) compared to the control group, paralleled by the pronounced differences (p < 0.01) observed with 5-fluorouracil.

| S-EPMC10974249 | biostudies-literature