scholarly journals Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1380
Author(s):  
Xiutao Wu ◽  
Lijie Gong ◽  
Chen Chen ◽  
Ye Tao ◽  
Wuxi Zhou ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Normal Cell ◽  
Selectivity Index ◽  
Cytotoxic Activities ◽  
Structure Activity ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Hct 116 ◽  
Systematic Structure

Harringtonolide (HO), a natural product isolated from Cephalotaxus harringtonia, exhibits potent antiproliferative activity. However, little information has been reported on the systematic structure−activity relationship (SAR) of HO derivatives. Modifications on tropone, lactone, and allyl positions of HO (1) were carried out to provide 17 derivatives (2–13, 11a–11f). The in vitro antiproliferative activity against four cancer cell lines (HCT-116, A375, A549, and Huh-7) and one normal cell line (L-02) was tested. Amongst these novel derivatives, compound 6 exhibited comparable cell growth inhibitory activity to HO and displayed better selectivity index (SI = 56.5) between Huh-7 and L-02 cells. The SAR results revealed that the tropone and lactone moieties are essential for the cytotoxic activities, which provided useful suggestions for further structural optimization of HO.

Synthesis, spectral, molecular modeling, biological and antitumor studies of new nifuroxazide complexes

2021 ◽  
Vol 11 (7) ◽  
pp. 1071-1083
Author(s):  
Eid H. Alosaimi ◽  
Walaa H. El-Shwiniy ◽  
Saad M. Alshahrani ◽  
Ayman A. O. Younes ◽  
Mostafa Y. Nassar ◽  
...  
Keyword(s):  
Bacterial Species ◽  
Thermal Analyses ◽  
Molar Conductance ◽  
Cancer Drug ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Anti Cancer ◽  
Hct 116 ◽  
Mcf 7

Series of Zr(IV), Ce(IV) and U(VI) complexes were synthesized with nifuroxazide ligand. Design and formulae of the complexes suggested in the light of analytical, spectral, magnetic and thermal analyses (1HNMR, IR, UV-Vis). The calculated values of molar conductance mean that, all isolated complexes were electrolytes. The data revealed the complexes formation and suggested that nifuroxazide binds as a bidentate at NO sites with metal ions. The kinetic parameters evaluated using Coats Redfern (CR) and Horowitz-Metzeger (HM) methods. The thermodynamic data reflect the thermal stability for all complexes. The calculated bond length and force constant values for UO2 bond are 1.741 Å and 459.409 Nm−1. The research investigations were related to quantum chemical calculations conducted at the theory level of DFT/B3LYP/LANL2DZ. The nifuroxazide, inorganic salts and their metal complexes were assayed against different bacterial species as well as the in vitro growth inhibitory activity against human breast carcinoma (MCF-7) and HCT-116 cell lines. Zr(IV) complex was found to have the highest activity against all the tested organisms and a powerful anti-cancer drug.

Synthesis, in-vitro cytotoxicity of 1H-benzo[f]chromene derivatives and structure–activity relationships of the 1-aryl group and 9-position

2017 ◽  
Vol 72 (5-6) ◽  
pp. 161-171 ◽  
Author(s):  
Hany M. Mohamed ◽  
Ahmed M. Fouda ◽  
Essam S.A.E.H. Khattab ◽  
Ahmed M. El- Agrody ◽  
Tarek H. Afifi
Keyword(s):  
Phenyl Ring ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Activities ◽  
Specific Group ◽  
Aryl Group ◽  
Sar Studies ◽  
Structure Activity ◽  
Hct 116 ◽  
Mcf 7

Abstract A series of 1H-benzo[f]chromene-2-carbonitriles was synthesized and evaluated for their cytotoxic activities against MCF-7, HCT-116, and HepG-2 cancer cells. The SAR studies reported that the substitution in the phenyl ring at 1-position of 1H-benzo[f]chromene nucleus with the specific group, H atom, or methoxy group at 9-position increases the ability of the molecule against the different cell lines.

scholarly journals Synthesis and Evaluation of the Antitumor Activity of Novel 1-(4-Substituted phenyl)-2-ethyl Imidazole Apoptosis Inducers In Vitro

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4293
Author(s):  
Zhen-Wang Li ◽  
Chun-Yan Zhong ◽  
Xiao-Ran Wang ◽  
Shi-Nian Li ◽  
Chun-Yuan Pan ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cells ◽  
Antiproliferative Activity ◽  
Antitumor Agent ◽  
Positive Control ◽  
Selectivity Index ◽  
Time Dependent ◽  
Potential Candidate ◽  
Dependent Manner

Novel imidazole derivatives were designed, prepared, and evaluated in vitro for antitumor activity. The majority of the tested derivatives showed improved antiproliferative activity compared to the positive control drugs 5-FU and MTX. Among them, compound 4f exhibited outstanding antiproliferative activity against three cancer cell lines and was considerably more potent than both 5-FU and MTX. In particular, the selectivity index indicated that the tolerance of normal L-02 cells to 4f was 23–46-fold higher than that of tumor cells. This selectivity was significantly higher than that exhibited by the positive control drugs. Furthermore, compound 4f induced cell apoptosis by increasing the protein expression levels of Bax and decreasing those of Bcl-2 in a time-dependent manner. Therefore, 4f could be a potential candidate for the development of a novel antitumor agent.

scholarly journals Plasmodium falciparum Line-Dependent Association ofIn VitroGrowth-Inhibitory Activity and Risk of Malaria

2012 ◽  
Vol 80 (5) ◽  
pp. 1900-1908 ◽  
Author(s):  
Josea Rono ◽  
Anna Färnert ◽  
Daniel Olsson ◽  
Faith Osier ◽  
Ingegerd Rooth ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Activity ◽  
Content Type ◽  
Phenotypic Differences ◽  
Erythrocyte Invasion ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Control Study

ABSTRACTPlasmodium falciparum's ability to invade erythrocytes is essential for its survival within the human host. Immune mechanisms that impair this ability are therefore expected to contribute to immunity against the parasite. Plasma of humans who are naturally exposed to malaria has been shown to have growth-inhibitory activity (GIA)in vitro. However, the importance of GIA in relation to protection from malaria has been unclear. In a case-control study nested within a longitudinally followed population in Tanzania, plasma samples collected at baseline from 171 individuals (55 cases and 116 age-matched controls) were assayed for GIA using threeP. falciparumlines (3D7, K1, and W2mef) chosen based on their erythrocyte invasion phenotypes. Distribution of GIA differed between the lines, with most samples inhibiting the growth of 3D7 and K1 and enhancing the growth of W2mef. GIA to 3D7 was associated with a reduced risk of malaria within 40 weeks of follow-up (odds ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.96;P= 0.04), whereas GIA to K1 and W2mef was not. These results show that GIA, as well as its association with protection from malaria, is dependent on theP. falciparumline and can be explained by differences in erythrocyte invasion phenotypes between parasite lines. Our study contributes knowledge on the biological importance of growth inhibition and the potential influence ofP. falciparumerythrocyte invasion phenotypic differences on its relationship to protective immunity against malaria.

scholarly journals Four New Pterosins from Pteris cretica and Their Cytotoxic Activities

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2767
Author(s):  
Jian Lu ◽  
Caiying Peng ◽  
Shuang Cheng ◽  
Jianqun Liu ◽  
Qinge Ma ◽  
...  
Keyword(s):  
Human Tumor ◽  
2D Nmr ◽  
Cytotoxic Activities ◽  
Aerial Parts ◽  
Pteris Cretica ◽  
Phytochemical Investigation ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
New Compounds

Phytochemical investigation of the aerial parts of Pteris cretica led to the isolation and elucidation of nine pterosins, including four new pterosins, creticolacton A (1), 13-hydroxy-2(R),3(R)-pterosin L (2), creticoside A (3), and spelosin 3-O-β-d-glucopyranoside (4), together with five known pterosins 5–9. Their structures were identified mainly on the basis of 1D and 2D NMR spectral data, ESI-MS and literature comparisons. Compounds 1 and 3 were new type of petrosins with a six membered ring between C-14 and C-15. The new compounds were tested in vitro for their cytotoxic activities against four human tumor cell lines (SH-SY5Y, SGC-7901, HCT-116, Lovo). Results showed that compounds 1 and 2 exhibited cytotoxic activity against HCT-116 cells with IC50 value of 22.4 μM and 15.8 μM, respectively.

scholarly journals Anti-Trypanosomal Alkaloids from Xymalos Monospora

2006 ◽  
Vol 1 (8) ◽  
pp. 1934578X0600100
Author(s):  
Dieudonne Ngamga ◽  
Pierre Tane ◽  
Donna Rattendi ◽  
Cyrus Bacchi ◽  
Christopher C. Okunji ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Stem Bark ◽  
Aporphine Alkaloid ◽  
African Trypanosomes ◽  
Benzylisoquinoline Alkaloids ◽  
Benzylisoquinoline Alkaloid ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

From an extract of the stem bark of Xymalos monospora, a bis-benzylisoquinoline alkaloid (1), three benzylisoquinoline alkaloids (mollinedine, 1-(p-methoxybenzyl)-6,7-methylenedioxyisoquino-line, doryafranine), and an aporphine alkaloid (N-methyllaurotetanine) were isolated. These compounds were tested for growth inhibitory activity against bloodstream forms of three strains of African trypanosomes. In vitro IC50 values starting from 1.8 μg /mL were obtained.

scholarly journals SAR:s for the Antiparasitic Plant Metabolite Pulchrol. 1. The Benzyl Alcohol Functionality

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3058 ◽  
Author(s):  
Paola Terrazas ◽  
Efrain Salamanca ◽  
Marcelo Dávila ◽  
Sophie Manner ◽  
Alberto Giménez ◽  
...  
Keyword(s):  
Natural Product ◽  
Qsar Model ◽  
Selectivity Index ◽  
Antiparasitic Activity ◽  
Molecular Features ◽  
Structure Activity ◽  
Plant Metabolite ◽  
Antiparasitic Agents ◽  
Positive Controls

Pulchrol (1) is a natural benzochromene isolated from the roots of Bourreria pulchra, shown to possess potent antiparasitic activity towards both Leishmania and Trypanozoma species. As it is not understood which molecular features of 1 are important for the antiparasitic activity, several analogues were synthesized and assayed. The ultimate goal is to understand the structure–activity relationships (SAR:s) and create a QSAR model that can be used for the development of clinically useful antiparasitic agents. In this study, we have synthesized 25 2-methoxy-6,6-dimethyl-6H-benzo[c]chromen analogues of 1 and its co-metabolite pulchral (5a), by semi-synthetic procedures starting from the natural product pulchrol (1) itself. All 27 compounds, including the two natural products 1 and 5a, were subsequently assayed in vitro for antiparasitic activity against Trypanozoma cruzi, Leishmania brasiliensis and Leishmania amazoniensis. In addition, the cytotoxicity in RAW cells was assayed, and a selectivity index (SI) for each compound and each parasite was calculated. Several compounds are more potent or equi-potent compared with the positive controls Benznidazole (Trypanozoma) and Miltefosine (Leishmania). The compounds with the highest potencies as well as SI-values are esters of 1 with various carboxylic acids.

Synthesis and antiproliferative activity of novel 4-azasteroidal-17-hydrazone derivatives

2019 ◽  
Vol 43 (3-4) ◽  
pp. 130-134
Author(s):  
Shao-Rui Chen ◽  
Hao Wu ◽  
Hai-Yan Zhao ◽  
Yu-Mei Zhang ◽  
Peng-Qi Li ◽  
...  
Keyword(s):  
Cell Line ◽  
Antiproliferative Activity ◽  
Normal Cell ◽  
Spectroscopic Data ◽  
Human Lung ◽  
Positive Control ◽  
Mucosal Cell ◽  
Human Gastric Adenocarcinoma ◽  
Normal Human

A new series of 4-azasteroidal-17-hydrazone derivatives have been synthesized from androstenedione. Their structures were characterized by analysis and spectroscopic data. The antiproliferative activity of synthesized compounds against three cancer cells (human lung adenocarcinoma, human oesophageal cervical cancer, human gastric adenocarcinoma) and a normal cell line (human gastric mucosal) was investigated. The studies show that the compound bearing a naphthyl group displayed the same antiproliferative activity in vitro against tested cells as cis-platin did (a positive control). Most of the compounds show very weak toxicity towards normal human gastric mucosal cell line.

scholarly journals Design and Synthesis of C-19 Isosteviol Derivatives as Potent and Highly Selective Antiproliferative Agents

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 121 ◽  
Author(s):  
Tian Luan ◽  
Li-Hua Cao ◽  
Hao Deng ◽  
Qing-Kun Shen ◽  
Yu-Shun Tian ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Human Cancer ◽  
Parent Compound ◽  
Cyclin A ◽  
Cyclin B1 ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cyclin E1 ◽  
Hct 116

Six series of novel isosteviol derivatives; modified in the C-19 position; were synthesized; and their antiproliferative activity was evaluated against three human cancer cell lines (HCT-116; BEL-7402; HepG2) and the human L02 normal cell line in vitro. Most of the derivatives tested here exhibited improved antiproliferative activity with high selectivity when compared with the parent compound isosteviol and the positive control drug 5-fluorouracil. Among these derivatives; compound 5d exhibited the most potent antiproliferative activity and commendable selectivity between cancer and normal cells. In addition; compound 5d inhibited the colony formation of HCT-116 cells in a concentration-dependent manner. Further studies revealed that compound 5d arrested the HCT-116 cell cycle in the S phase; and western blot analysis demonstrated the mechanism may be correlated with a change in the expression of cyclin A; cyclin B1; and cyclin E1. Furthermore; the results of a docking study that involved placing compound 5d into the CDK2/cyclin A binding site revealed that its mode of action was possibly as a CDK2/cyclin A inhibitor.

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