scholarly journals Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 737
Author(s):  
Elwira Chrobak ◽  
Maria Jastrzębska ◽  
Ewa Bębenek ◽  
Monika Kadela-Tomanek ◽  
Krzysztof Marciniec ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Cell Lines ◽  
Human Cancer ◽  
Amelanotic Melanoma ◽  
Human Cancer Cell Lines ◽  
Ic50 Values ◽  
C 32 ◽  
New Compounds ◽  
Derivatives Of

A series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activities of the new compounds were also compared with their 29-phosphonate analogs. Compounds 7a and 7b showed the highest activity against C-32 and SNB-19 cell lines. The IC50 values for 7a were 2.15 and 0.91 μM, and, for 7b, they were 0.76 and 0.8 μM for the C-32 and SNB-19 lines, respectively. The most potent compounds, 7a and 7b, were tested for their effects on markers of apoptosis, such as H3, TP53, BAX, and BCL-2. For the whole series of phosphate derivatives, a lipophilicity study was performed, and the ADME parameters were calculated. The most active products were docked to the active site of the EGFR protein. The relative binding affinity of selected phosphate betulin derivatives toward EGFR was compared with standard erlotinib on the basis of ChemScore and KDEEP score. Positively, all derivatives docked inside the cavity and showed significant interactions. Moreover, a molecular dynamics study also reveals that ligands 7a,b form stable complexes and the plateau phase started after 7 ns.

Synthesis and Cytotoxicity Assessment of Novel 7-O- and 14-O-Derivatives of Glaucocalyxin A

2020 ◽  
Vol 20 (10) ◽  
pp. 1241-1249
Author(s):  
Hong-Chuan Liu ◽  
Li-Ming Qiao ◽  
Wei Zheng ◽  
Zhao-Bao Xiang ◽  
Hai-Sheng Chen ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Folk Medicine ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Human Cancer Cell Lines ◽  
Derivatives Of

Background: Rabdosia japonica has been historically used in China as a popular folk medicine for the treatment of cancer, hepatitis, and gastricism. Glaucocalyxin A (GLA), an ent-kaurene diterpene isolated from Rabdosia japonica, is one of the main active ingredients showing potent inhibitory effects against several types of tumor cells. To the best of our knowledge, studies regarding the structural modification and Structure- Activity Relations (SAR) of this compound have not yet been reported. Objective: The aim of this study was to discover more potent derivatives of GLA and investigate their SAR and cytotoxicity mechanisms. Methods: Novel 7-O- and 14-O-derivatives of GLA were synthesized by condensation of acids or acyl chloride. The anti-tumor activities of these derivatives against various human cancer cell lines were evaluated in vitro by MTT assays. Apoptosis assays of compound 17 (7,14-diacylation product) were performed on A549 and HL-60 cells by flow cytometry and TUNNEL. The acute toxicity of this compound was tested on mice, at the dose of 300mg per kg body weight. Results: Seventeen novel 7-O- and 14-O-derivatives of GLA (1-17) were synthesized. These compounds showed potent cytotoxicity against the tested cancer cell lines, and almost all of them were found to be more cytotoxic than GLA and oridonin. Of the synthesized derivatives, compound 17 presented the greatest cytotoxicity, with IC50 values of 0.26μM and 1.10μM in HL-60 and CCRF-CEM cells, respectively. Furthermore, this compound induced weak apoptosis of A549 cells but showed great potential in stimulating the apoptosis of HL- 60 cells. Acute toxicity assays indicated that compound 17 is relatively safer. Conclusion: The results reported herein indicate that the synthesized GLA derivatives exhibited greater cytotoxicity against leukemia cells than against other types of tumors. In particular, 7,14-diacylation product of GLA was found to be an effective anti-tumor agent. However, the cytotoxicity mechanism of this product in A549 cells is expected to be different than that in other tumor cell lines. Further research is needed to confirm this hypothesis.

Six New neo-Clerodane Diterpenoids from Aerial Parts of Scutellaria barbata and Their Cytotoxic Activities

Planta Medica ◽  
2018 ◽  
Vol 84 (17) ◽  
pp. 1292-1299 ◽  
Author(s):  
Guo-Chun Yang ◽  
Jia-Hui Hu ◽  
Bing-Long Li ◽  
Huan Liu ◽  
Jia-Yue Wang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cancer ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Activities ◽  
Scutellaria Barbata ◽  
Human Cancer Cell Lines ◽  
Aerial Parts ◽  
Ic50 Values ◽  
Clerodane Diterpenoids

AbstractSix new neo-clerodane diterpenoids (1–6), scutebatas X – Z, A1-C1, along with twelve known ones (7–18) were obtained via the phytochemical investigation of the aerial parts of Scutellaria barbata. Their structures were established by detailed spectroscopic analysis. The absolute configurations of 1 and 2, as the representative members of this type, were identified based on a circular dichroic exciton chirality method. Moreover, in vitro cytotoxicity of compounds 1–6 were evaluated against three human cancer cell lines (SGC-7901, MCF-7, and A-549) using the MTT method. Compound 6 showed cytotoxic activities against all the three cell lines with IC50 values of 17.9, 29.9, and 35.7 µM, respectively.

scholarly journals Synthesis of Novel Benzamide- piperazine-sulfonamide Hybrids as Potential Anticancer Agents

2019 ◽  
Vol 92 (3) ◽  
pp. 393-402
Author(s):  
B. Ramalingeswara Rao ◽  
Mohana Rao Katiki ◽  
Dileep Kommula ◽  
SaiShyam Narayanan ◽  
Ruby John Anto ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
In Vitro Cytotoxicity ◽  
Sensitive Cell Line ◽  
Human Cancer Cell Lines ◽  
Ic50 Values ◽  
Different Origins ◽  
New Compounds ◽  
A549 Lung

The synthesis of a series of substituted hippuric acid (2-benzamidoacetic acid) derivatives containing arylsulfonylpiperazine nucleus (3a–j, 4a–j) is described. The compounds were synthesized by coupling hippuric/4-fluorohippuric acid with various arylsulfonylpiperazines using N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDCI). The structures of all the new compounds were confirmed by IR, NMR and MS spectral data. All the synthesized compounds have been evaluated for their in vitro cytotoxicity towards five human cancer cell lines of different origins viz. HeLa (Cervical), A549 (Lung), A375 (Skin), MD-AMB-231(Breast) and T98G (brain) and their IC50 values were determined. Among the compounds tested, 3b, 3d, 3g, 4c and 4e displayed significant cytotoxic activity (IC50 = 24.2–38.2 µM). T98G was the most sensitive cell line towards the compounds studied followed by HeLa, A375, A549 and MD-AMB-231.

scholarly journals Two New Cytotoxic Steroidal Alkaloids from Sarcococca Hookeriana

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 11 ◽  
Author(s):  
Shaojie Huo ◽  
Jichun Wu ◽  
Xicheng He ◽  
Lutai Pan ◽  
Jiang Du
Keyword(s):  
Cell Lines ◽  
Human Cancer ◽  
Cytotoxic Activities ◽  
Steroidal Alkaloids ◽  
X Ray ◽  
Human Cancer Cell Lines ◽  
X Ray Crystallography ◽  
Ic50 Values ◽  
Mcf 7

Two new steroidal alkaloids, named hookerianine A (1) and hookerianine B (2) were isolated from the stems and roots of Sarcococca hookeriana Baill., along with two known compounds, sarcorucinine G (3) and epipachysamine D (4). On the basis of spectroscopic methods and by comparison with literature data, their structures were determined. As well as X-ray crystallography was performed to confirm compound 4. To identify novel antitumor inhibitors, all compounds were performed a CCK-8 assay against five human cancer cell lines SW480, SMMC-7721, PC3, MCF-7 and K562 in vitro. Compound 2 exhibited moderate cytotoxic activities to all cell lines with IC50 values in the range of 5.97–19.44 μM. Compound 3 was the most effective one against SW480 and K562 cell lines with IC50 values of 5.77 and 6.29 μM, respectively.

scholarly journals Design, Synthesis and Characterization of Novel Amine Derivatives of 5-[5-(Chloromethyl)-1, 3, 4-Oxadiazol-2-yl]- 2-(4-Fluorophenyl)-Pyridine as a New Class of Anticancer Agents

2017 ◽  
Vol 16 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Adimule Vinayak ◽  
Medapa Sudha ◽  
Kumar S Lalita
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Secondary Amines ◽  
Design Synthesis ◽  
Human Cancer Cell Lines ◽  
Ic50 Values ◽  
High Cytotoxicity ◽  
Hepg2 Cell Lines

A linear strategy was adopted in synthesizing the novel amine derivatives 7(a-h) of 5-[5- (chloromethyl)-1, 3, 4-oxadiazol-2-yl]-2-(4-fluorophenyl)-pyridine (6) and screened these compounds for in vitro anticancer activity against three human cancer cell lines (HeLa,Caco-2 and HepG2). The synthesised novel compounds were characterized by 1H NMR, MS and 13C NMR spectroscopic evidences. Microwave irradiation of compound (5) in presence of chloroacetyl chloride and phosphoryl oxychloride yielded the dehydrated cyclized key intermediate 5-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]-2-(4-fluorophenyl)-pyridine which upon treatment with various primary or secondary amines (a-h) resulted into the corresponding amine derivatives. The IC50 values of the final compounds were compared with that of 5-fluorouracil (5-FU) taken as the standard. Compounds 7a and 7d were found to be highly cytotoxic against HepG2 cell lines with IC50 values of 2.6 ?M (IC50 = 34.0 ± 0.5 ?M) and 5.8 ?M (IC50 = 112 ± 1.4 ?M) respectively. The compound (7f) alone was found to have high cytotoxicity against Caco-2 cell lines with IC50 value of 2.3 ?M (IC50 = 87 ± 2.6 ?M).Dhaka Univ. J. Pharm. Sci. 16(1): 11-19, 2017 (June)

scholarly journals Design, Synthesis and Evaluation of New Bioactive Oxadiazole Derivatives as Anticancer Agents Targeting Bcl-2

2020 ◽  
Vol 21 (23) ◽  
pp. 8980
Author(s):  
Rania Hamdy ◽  
Samia A. Elseginy ◽  
Noha I. Ziedan ◽  
Mohamed El-Sadek ◽  
Elsaid Lashin ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Phosphorus Oxychloride ◽  
Human Cancer ◽  
Acid Hydrazide ◽  
Positive Control ◽  
Human Cancer Cell Lines ◽  
Ic50 Values

A series of 2-(1H-indol-3-yl)-5-substituted-1,3,4-oxadiazoles, 4a–m, were designed, synthesized and tested in vitro as potential pro-apoptotic Bcl-2 inhibitory anticancer agents based on our previously reported hit compounds. Synthesis of the target 1,3,4-oxadiazoles was readily accomplished through a cyclization reaction of indole carboxylic acid hydrazide 2 with substituted carboxylic acid derivatives 3a–m in the presence of phosphorus oxychloride. New compounds 4a–m showed a range of IC50 values concentrated in the low micromolar range selectively in Bcl-2 positive human cancer cell lines. The most potent candidate 4-trifluoromethyl substituted analogue 4j showed selective IC50 values of 0.52–0.88 μM against Bcl-2 expressing cell lines with no inhibitory effects in the Bcl-2 negative cell line. Moreover, 4j showed binding that was two-fold more potent than the positive control gossypol in the Bcl-2 ELISA binding affinity assay. Molecular modeling studies helped to further rationalize anti-apoptotic Bcl-2 binding and identified compound 4j as a candidate with drug-like properties for further investigation as a selective Bcl-2 inhibitory anticancer agent.

scholarly journals Synthesis, Structure and Cytotoxicity Testing of Novel 7-(4,5-Dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-Imine Derivatives

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5924
Author(s):  
Łukasz Balewski ◽  
Franciszek Sączewski ◽  
Patrick J. Bednarski ◽  
Lisa Wolff ◽  
Anna Nadworska ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Spectroscopic Data ◽  
Human Cancer ◽  
Human Cancer Cell ◽  
X Ray ◽  
Human Cancer Cell Lines ◽  
Ic50 Values

The appropriate 1-arylhydrazinecarbonitriles 1a–c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a–c, which are subsequently converted into the corresponding amides 4a–e, 8a–c, sulfonamides 5a–n, 9, ureas 6a–I, and thioureas 7a–d. The structures of the newly prepared derivatives 3a–c, 4a–e, 5a–n, 6a–i, 7a–d, 8a–c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-[1,1′-biphenyl]-4-sulfonamide (5l) inhibits the growth of the cervical cancer SISO and bladder cancer RT-112 cell lines with IC50 values in the range of 2.38–3.77 μM. Moreover, N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-phenyl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-4-phenoxybenzenesulfonamide (5m) has the best selectivity towards the SISO cell line and induces apoptosis in this cell line.

Design, Synthesis and In vitro Cytotoxic Evaluation of Novel Hybrids of Artemisinin and Quinazolinone

2021 ◽  
Vol 18 ◽  
Author(s):  
Tran Khac Vu ◽  
Bach Xuan Nguyen ◽  
Linh Nguyen Pham Duy ◽  
Thuc Bao Nguyen Truong ◽  
Anh Tuan Phung ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Anti Cancer ◽  
Ic50 Values ◽  
Mcf 7

Background: In this study, two novel hybrid series of artemisinin and quinazolinones were synthesized and evaluated in vitro cytotoxicity against two human cancer cell lines, including SKLu-1 (lung cancer), MCF- 7 (breast cancer). The bio-assay results indicated that most of the target compounds exhibited cytotoxic activities against both human cancer cell lines tested, and seemed to be more cytotoxic toward the breast (MCF-7) cancer cells than lung (SKLu-1) cancer cells. Among the synthesized artemisinin hybrids, the compound 13d containing a quinazolinone conjugated system exhibited the most potent cytotoxicity against the SKLu-1 and MCF-7 cell lines with IC50 values of 1.62 and 0.77 µM, respectively. Objective: This study aims at developing novel hybrids of artemisinin and quinazolinones as anti-cancer agents. Method: A series of novel hybrids were designed, synthesized and evaluated for cytotoxicity against two human cancer cell lines, including SKLu-1 and MCF-7 using SRB method. Results : All thirteen hybrids of artemisinin with quinazolinone exhibited cytotoxic activity against two tested cancer cell lines, in which the compound 13d exhibited the most potent cytotoxicity against the SKLu-1 and MCF-7 cell lines with IC50 values of 1.62 and 0.77 µM, respectively. Conclusion: The research results suggest that some compounds could be considered as leads for future design of hybrids and have the potential for further studies in the field of anti-cancer agent development.

scholarly journals Synthesis and Cytotoxic Evaluation of Novel Ester Derivatives of Betulin with AZT, d4T, and 3TC

2017 ◽  
Vol 12 (6) ◽  
pp. 1934578X1701200
Author(s):  
Dang Thi Tuyet Anh ◽  
Le Nhat Thuy Giang ◽  
Nguyen Thi Hien ◽  
Dinh Thi Cuc ◽  
Nguyen Ha Thanh ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Antitumor Activities ◽  
Human Cancer Cell Lines ◽  
Anticancer Properties ◽  
Derivatives Of

Novel ester derivatives of betulin with AZT, d4T, and 3TC were synthesized and assessed for antitumor activities against the KB and HepG2 human cancer cell lines in vitro by MTT assay. Some derivatives displayed high anticancer properties, with IC50 values between 1 and 21 μM on the two cancer cell lines.

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