Cytotoxic Activity
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2021 ◽  
Vol 14 ◽  
Emeline Cros-Perrial ◽  
Steve Saulnier ◽  
Muhammad Zawwad Raza ◽  
Rémi Charmelot ◽  
David Egron ◽  

Background: The development of small molecules as cancer treatments is still of both interest and importance. Objective: Having synthesized and identified the initial cytotoxic activity of a series of chemically related N-(9H-purin-6-yl) benzamide derivatives, we continued their evaluation on cancer cell models. We also synthesized water-soluble prodrugs of the main compound and performed in vivo experiments. Method: We used organic chemistry to obtain compounds of interest and prodrugs. The biological evaluation included MTT assays, synergy experiments, proliferation assays by CFSE, cell cycle distribution and in vivo antitumoral activity. Results: Our results show activities on cancer cell lines ranging from 3-39 µM for the best compounds, with both induction of apoptosis and decrease in cell proliferation. Two compounds evaluated in vivo showed weak antitumoral activity. In addition, the lead compound and its prodrug had a synergistic activity with the nucleoside analogue fludarabine in vitro and in vivo. Conclusion: Our work allowed us to gain better knowledge on the activity of N-(9H-purin-6-yl) benzamide derivatives and showed new examples of water-soluble prodrugs. More research is warranted to decipher the molecular mechanisms of the molecules.

Deyzi Caroline da Silva Barbosa ◽  
Vanderlan Nogueira Holanda ◽  
Arabinda Ghosh ◽  
Rafael Trindade Maia ◽  
Welson Vicente da Silva ◽  

Plants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2156
Reda F. A. Abdelhameed ◽  
Sameh S. Elhady ◽  
Alaa Sirwi ◽  
Hanan Samir ◽  
Elsayed A. Ibrahim ◽  

The current study was designed to investigate the antioxidant and cytotoxic activities of Thonningia sanguinea whole-plant extract. The total phenolic content was determined using Folin–Ciocalteu reagent and found to be 980.1 mg/g, calculated as gallic acid equivalents. The antioxidant capacity was estimated for the crude extract and the phenolic portion of T. sanguinea, whereupon both revealed a dose-dependent scavenging rate of DPPH• with EC50 values of 36.33 and 11.14 µg/mL, respectively. Chemical profiling of the plant extract was achieved by LC-ESI-TOF-MS/MS analysis, where 17 compounds were assigned, including ten compounds detected in the negative mode and seven detected in the positive mode. The phenolic portion exhibited promising cytotoxic activity against MCF-7 and HepG2 cells, with IC50 values of 16.67 and 13.51 μg/mL, respectively. Phenolic extract treatment caused apoptosis in MCF-7 cells, with total apoptotic cell death 18.45-fold higher compared to untreated controls, arresting the cell cycle at G2/M by increasing the G2 population by 39.7%, compared to 19.35% for the control. The apoptotic investigation was further validated by the upregulation of proapoptotic genes of P53, Bax, and caspases-3,8 9, and the downregulation of Bcl-2 as the anti-apoptotic gene. Bcl-2 inhibition was also virtualized by good binding interactions through a molecular docking study. Taken together, phenolic extract exhibited promising cytotoxic activity in MCF-7 cells through apoptosis induction and antioxidant activation, so further fractionation studies are recommended for the phenolic extract for specifying the most active compound to be developed as a novel anti-cancer agent.

Sani Ega Priani ◽  
Tia Nur Setianty ◽  
Ratih Aryani ◽  
Sri Peni Fitrianingsih ◽  
Livia Syafnir

Background: The incidence and mortality of cancer are rapidly growing worldwide. Modification on drug delivery systems based on nanotechnology was applied to improve the effectiveness and safety of treatment. Nanoencapsulation, a part of nanotechnology,  was known can be involved in cytotoxic agents. Objective: This research was conducted to determine the type of polymers for nanoencapsulation of cytotoxic agents and analyze the effect of nanoencapsulation on the cytotoxic activity. Methods: The study was performed by systematic literature review using selected articles from reputable databases that meet the inclusion and exclusion criteria. Results: The results show that many cytotoxic agents have been developed in nanocapsules systems due to their low water solubility, chemical instability, and low bioavailability. The nanoencapsulation process was carried out using synthetic or natural polymers such as polylactic-co-glycolic acid (PLGA), PEGylated PLGA, polycaprolactone (PCL), chitosan-sodium tripolyphosphate, chitosan-sodium alginate, heparin-poly(l-lysine), and polymethyl methacrylate (PMMA). Those polymers are widely used for nanoencapsulation related to their biocompatible, biodegradable, non-toxic, and providing the desired coating properties. The nanoencapsulation on cytotoxic agents significantly increases the in vitro cytotoxicity, marked by the decrease of IC50 value in the range 1.4-15.4 folds compared to pure drugs. The increase in cytotoxicity could be caused by particle size reduction, modification of particle surface properties, and enhancement of drug stability. Conclusion: It can be concluded that nanoencapsulation can be applied for cytotoxic agents to increase their activity using the appropriate coating polymer.

Mariana N. Costa ◽  
Roberto N. Silva

Polyhedron ◽  
2021 ◽  
pp. 115504
Dhrubajyoti Majumdar ◽  
Burak Tüzün ◽  
Tapan Kumar Pal ◽  
Reena V. Saini ◽  
Kalipada Bankura ◽  

Raneem Jatal ◽  
Rihab Osman ◽  
Wael Mamdouh ◽  
Gehanne A.S. Awad

2021 ◽  
Febri Wulandari ◽  
Muthi' Ikawati ◽  
Mitsunori Kirihata ◽  
Sitarina Widyarini ◽  
Jun-Ya Kato ◽  

Abstract Pentagamavunone-1 and its newest derivatives, CCA-1.1, possess an outstanding cytotoxic activity against several cancer cell lines, especially colorectal cancer. We are continuing to explore the anti-colorectal cancer properties of PGV-1 and CCA-1.1 against DMH-induced colorectal cancer rats and expound the potential protein target in colorectal adenocarcinoma. We utilized DMH 60 mg/kg (subcutaneous injection once a week for 16 weeks) to induce colorectal cancer. PGV-1 and CCA-1.1 at 10 and 20 mg/kg (orally twice a week for 16 weeks) were co-administered with DMH. The WBC count increased in a single DMH group and was countered by co-administration of PGV-1 and CCA-1.1, but no significant differences in RBC. Single DMH treatment for 16 weeks resulted in 80% adenocarcinoma. In contrast, co-administration with PGV-1 and CCA-1.1 suppressed most of the carcinogenic characteristics and symptoms of the pre-malignancy condition. Furthermore, bioinformatics analysis showed that CCA-1.1 has more specific targets than PGV-1, including CDK1, CDK2, MMP3, MMP14, and CYP3A4, which regulate the cell cycle arrest, cancer cell migration, and xenobiotic metabolism, respectively. Interestingly, CCA-1.1 targets CYP3A4, which possibly interrupts DMH metabolism and prevents the initiation of DMH-colorectal carcinogenesis. In conclusion, CCA-1.1 performed better chemopreventive effects against DMH colorectal cancer and might replace PGV-1 to be promoted as a more effective anti-colorectal cancer agent.

2021 ◽  
Vol 50 (9) ◽  
pp. 2663-2674
Iwan Dini ◽  
Nunuk Hariani Soekamto ◽  
Firdaus Firdaus ◽  
Unang Supratman ◽  
Jalifah Latip

Alkaloid caulerpin (1), along with β-sitosterol (2), were isolated from the n-hexane extract of the macroalga Halimeda cylindracea Decaisne. The chemical structure was identified by a spectroscopic method including IR, MS, UV, NMR 1D, NMR 2D, and comparison with data of spectra previously reported. Compounds (1) and (2) were isolated for the first time from this macroalga. Compund (1) were evaluated for their cytotoxicity activity against NCL-H460 lung cancer cells in vitro and showed moderate activity with IC50 value of 20.05 µg/mL.

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5827
Hamdoon A. Mohammed ◽  
Mohammed F. Abd El-Wahab ◽  
Usama Shaheen ◽  
Abd El-Salam I. Mohammed ◽  
Ashraf N. Abdalla ◽  

Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O-methylated flavonoids; 5,4’-dihydroxy-3,6,7-tri-O-methyl flavone (penduletin) (1), 5,3’-dihydroxy-3,6,7,4’,5’-penta-O-methyl flavone (2), and 5-hydroxy-3,6,7,3’,4’,5’-hexa-O-methyl flavone (3) from Rhamnus disperma roots. Additionlly, four flavonoid glycosides; kampferol 7-O-α-L-rhamnopyranoside (4), isorhamnetin-3-O-β-D-glucopyranoside (5), quercetin 7-O-α-L-rhamnopyranoside (6), and kampferol 3, 7-di-O-α-L-rhamnopyranoside (7) along with benzyl-O-β-D-glucopyranoside (8) were successfully isolated. Complete structure characterization of these compounds was assigned based on NMR spectroscopic data, MS analyses, and comparison with the literature. The O-methyl protons and carbons of the three O-methylated flavonoids (1–3) were unambiguously assigned based on 2D NMR data. The occurrence of compounds 1, 4, 5, and 8 in Rhamnus disperma is was reported here for the first time. Compound 3 was acetylated at 5-OH position to give 5-O-acetyl-3,6,7,3’,4’,5’-hexa-O-methyl flavone (9). Compound 1 exhibited the highest cytotoxic activity against MCF 7, A2780, and HT29 cancer cell lines with IC50 values at 2.17 µM, 0.53 µM, and 2.16 µM, respectively, and was 2–9 folds more selective against tested cancer cell lines compared to the normal human fetal lung fibroblasts (MRC5). It also doubled MCF 7 apoptotic populations and caused G1 cell cycle arrest. The acetylated compound 9 exhibited cytotoxic activity against MCF 7 and HT29 cancer cell lines with IC50 values at 2.19 µM and 3.18 µM, respectively, and was 6–8 folds more cytotoxic to tested cancer cell lines compared to the MRC5 cells.

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