scholarly journals Design, Synthesis, and Cell Lines Studies of Oleanolic Acid—Hydrogen Sulfide Donor Hybrids

2021 ◽  
Vol 11 (8) ◽  
pp. 3364
Author(s):  
Fenqin Zhao ◽  
Jinyu Li ◽  
Kexin Yue ◽  
Beibei Song ◽  
Erying Sun ◽  
...  
Keyword(s):  
Cell Lines ◽  
Oleanolic Acid ◽  
Cancer Cell ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Design Synthesis ◽  
Anti Cancer ◽  
First Time ◽  
Donor Moiety

In order to develop new oleanolic acid (OA) derivatives endowed with improved antitumor activities, for the first time, a number of new hybrid compounds were reported by combining OA or 3-oxooleanolic acid with appropriate H2S-donor moiety, coupled via a suitable linker. The anti-tumor evaluation indicated that they exhibited excellent anti-cancer activities against the tested cancer cell lines. Moreover, 18d with 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H2S donor and β-alanine as the linker, showed more potent cytotoxicity against the tested cancer cell lines than OA and 3-oxooleanolic acid, especially for A549 cells. Furthermore, the preferred compound, 18d, preferentially accumulates in cancer cells (13.6 μM) over the matched normal cells LO2 (>100 μM) in vitro. The improved antitumor activity of this hybrid was probably due to its H2S-releasing capability.

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.

scholarly journals Pharmacoinformatics and Preclinical Studies of NSC765690 and NSC765599, Potential STAT3/CDK2/4/6 Inhibitors with Antitumor Activities against NCI60 Human Tumor Cell Lines

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 92
Author(s):  
Bashir Lawal ◽  
Yen-Lin Liu ◽  
Ntlotlang Mokgautsi ◽  
Harshita Khedkar ◽  
Maryam Rachmawati Sumitra ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Tumor ◽  
Cancer Cell Lines ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Anti Cancer

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis and cell survival and are widely implicated in tumor progression. In this study, we used the well-characterized US National Cancer Institute 60 (NCI60) human tumor cell lines to screen the in vitro anti-cancer activities of our novel small molecule derivatives (NSC765690 and NSC765599) of salicylanilide. Furthermore, we used the DTP-COMPARE algorithm and in silico drug target prediction to identify the potential molecular targets, and finally, we used molecular docking to assess the interaction between the compounds and prominent potential targets. We found that NSC765690 and NSC765599 exhibited an anti-proliferative effect against the 60 panels of NCI human cancer cell lines, and dose-dependent cytotoxic preference for NSCLC, melanoma, renal, and breast cancer cell lines. Protein–ligand interactions studies revealed that NSC765690 and NSC765599 were favored ligands for STAT3/CDK2/4/6. Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. NSC765690 and NSC765599 met the required safety and criteria of a good drug candidate, and are thus worthy of further in-vitro and in-vivo investigations in tumor-bearing mice to assess their full therapeutic efficacy.

scholarly journals Design, Synthesis and Biological Evaluation of a New Series of 1-Aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea Derivatives as Antiproliferative Agents

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2108 ◽  
Author(s):  
Chuanming Zhang ◽  
Xiaoyu Tan ◽  
Jian Feng ◽  
Ning Ding ◽  
Yongpeng Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Urea Derivatives ◽  
Antiproliferative Agents

To discover new antiproliferative agents with high efficacy and selectivity, a new series of 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea derivatives (7a–7t) were designed, synthesized and evaluated for their antiproliferative activity against A549, HCT-116 and PC-3 cancer cell lines in vitro. Most of the target compounds demonstrated significant antiproliferative effects on all the selective cancer cell lines. Among them, the target compound, 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-{4-{{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}thio}phenyl}urea (7i) was identified to be the most active one against three cell lines, which was more potent than the positive control with an IC50 value of 1.53 ± 0.46, 1.11 ± 0.34 and 1.98 ± 1.27 μM, respectively. Further cellular mechanism studies confirmed that compound 7i could induce the apoptosis of A549 cells in a concentration-dependent manner and elucidated compound 7i arrests cell cycle at G1 phase by flow cytometry analysis. Herein, the studies suggested that the 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea skeleton might be regarded as new chemotypes for designing effective antiproliferative agents.

The In Vitro Anti-Cancer Activities of 17βH-Neriifolin Isolated from Cerbera odollam and its Binding Activity on Na+, K+-ATPase

2020 ◽  
Vol 21 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Nurhanan M. Yunos ◽  
Asiah Osman ◽  
Muhammad H. Jauri ◽  
Nor J. Sallehudin ◽  
Siti Syarifah Mohd Mutalip
Keyword(s):  
Cell Death ◽  
Binding Energy ◽  
Cell Lines ◽  
Malachite Green ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Α Subunit ◽  
Anti Cancer ◽  
Malachite Green Assay

Background: 17βH-neriifolin, a cardiac glycoside compound had been successfully isolated from Cerbera odollam leaves based on the bioassay guided-isolation procedure. The aim of these studies were to determine the in vitro anti-cancer and binding effects of 17βH-neriifolin on Na+, K+-ATPase. Methods: The in vitro anti-cancer effects were evaluated using Sulphorhodamine B and Hoescht 33342 assays. The Na+, K+-ATPase assay was carried out using Malachite Green assay. In silico molecular docking studies and in vitro malachite green assay were used to predict the binding activities of 17βH-neriifolin on Na+, K+-ATPase and ouabain was also included as for comparison studies. Results: The compound was tested against breast (MCF-7, T47D), colorectal (HT-29), ovarian (A2780, SKOV-3) and skin (A375) cancer cell lines that gave IC50 values ranged from 0.022 ± 0.0015 to 0.030 ± 0.0018 μM. The mechanism of cell death of 17βH-neriifolin was further evaluated using Hoescht 33342 assay and it was found that the compound killed the cancer cells via apoptosis. 17βHneriifolin and ouabain both bound at α-subunit in Na+, K+-ATPase and their binding energy were - 8.16 ± 0.74 kcal/mol and -8.18 ± 0.48 kcal/mol respectively. Conclusion: The results had confirmed the anti-proliferative effects exerted by 17βH-neriifolin in the breast, colorectal, ovarian and skin cancer cell lines. 17βH-neriifolin had shown to cause apoptotic cell death in the respective cancer cell lines.17βH-neriifolin and ouabain both bound at α-subunit in Na+, K+-ATPase and their binding energy were -8.16 ± 0.74 kcal/mol and -8.18 ± 0.48 kcal/mol respectively. This is the first report to reveal that 17βH-neriifolin managed to bind to the pocket of α-subunit of Na+.K+-ATPase.

Design, Synthesis, and Cytotoxic Activity of New Tubulysin Analogues

Synlett ◽  
2021 ◽  
Author(s):  
Anh Tuan Tran ◽  
Chien Van Tran ◽  
Hai Van Le ◽  
Loc Van Tran ◽  
Thao Thi Phuong Tran ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Design Synthesis ◽  
Human Cancer Cell Lines ◽  
Ht 29

AbstractSynthesis of tubulysin analogues, containing an N-methyl substituent on tubuvaline-amide together with the replacement of either the hydrophobic N-terminal N-methyl pipecolic acid (Mep) or at both N- and C- terminal peptides with available heteroaromatic acids and an unsaturated tubuphenylalanine moiety, respectively, were described. The in vitro cytotoxic activity by SRB assay on five cancer cell lines for sixteen tubulysins was evaluated. Among them, five analogues exhibited strong cytotoxic activities against five human cancer cell lines, including human breast carcinoma (MCF7), human colorectal adenocarcinoma (HT-29), HL-60, SW-480, human lung adenocarcinoma (A459). Interestingly, one analogue showed the strongest cytotoxicity on all five tested cell lines even much higher toxicity than the reference compound ellipticine.

scholarly journals Design and Synthesis of Flavonoidal Ethers and Their Anti-Cancer Activity In Vitro

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1749 ◽  
Author(s):  
Lu Jin ◽  
Meng-Ling Wang ◽  
Yao Lv ◽  
Xue-Yi Zeng ◽  
Chao Chen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Hydroxyl Groups ◽  
Drug Candidates ◽  
Design And Synthesis ◽  
Anti Cancer ◽  
Clinical Drugs

Flavonoids are well-characterized polyphenolic compounds with pharmacological and therapeutic activities. However, most flavonoids have not been developed into clinical drugs, due to poor bioavailability. Herein, we report a strategy to increase the drugability of flavonoids by constructing C(sp2)-O bonds and stereo- as well as regioselective alkenylation of hydroxyl groups of flavonoids with ethyl-2,3-butadienoate allenes. Twenty-three modified flavonoid derivatives were designed, synthesized, and evaluated for their anti-cancer activities. The results showed that compounds 4b, 4c, 4e, 5e, and 6b exhibited better in vitro inhibitory activity against several cancer cell lines than their precursors. Preliminary structure–activity relationship studies indicated that, in most of the cancer cell lines evaluated, the substitution on position 7 was essential for increasing cytotoxicity. The results of this study might facilitate the preparation or late-stage modification of complex flavonoids as anti-cancer drug candidates.

scholarly journals Design, Synthesis, and In Vitro Antiproliferative Activity of Hydantoin and Purine Derivatives with the 4-Acetylphenylpiperazinylalkyl Moiety

Materials ◽  
2021 ◽  
Vol 14 (15) ◽  
pp. 4156
Author(s):  
Agnieszka Zagórska ◽  
Anna Czopek ◽  
Anna Jaromin ◽  
Magdalena Mielczarek-Puta ◽  
Marta Struga ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Docking Studies ◽  
Chemical Diversity ◽  
Cancer Drug ◽  
Purine Derivatives ◽  
Design Synthesis ◽  
Cancer Drug Discovery

Cancer represents one of the most serious health problems and the second leading cause of death around the world. Heterocycles, due to their prevalence in nature as well as their structural and chemical diversity, play an immensely important role in anti-cancer drug discovery. In this paper, a series of hydantoin and purine derivatives containing a 4-acetylphenylpiperazinylalkyl moiety were designed, synthesized, and biologically evaluated for their anticancer activity on selected cancer cell lines (PC3, SW480, SW620). Compound 4, a derivative of 3′,4′-dihydro-2′H-spiro[imidazolidine-4,1′-naphthalene]-2,5-dione, was the most effective against SW480, SW620, and PC3 cancer cell lines. Moreover, 4 has high tumor-targeting selectivity. Based on docking studies, it was concluded that R isomers of 3′,4′-dihydro-2′H-spiro[imidazolidine-4,1′-naphthalene]-2,5-dione could be further studied as promising scaffolds for the development of thymidine phosphorylase inhibitors.

Synthesis, antibacterial, and cytotoxicity evaluation of oleanolic acid-4-aminoquinoline based hybrid compounds

2021 ◽  
Vol 16 ◽  
Author(s):  
Vuyolwethu Khwaza ◽  
Opeoluwa O. Oyedeji ◽  
Blessing A. Aderibigbe ◽  
Eric Morifi ◽  
Y.T. Fonkui ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Oleanolic Acid ◽  
Cancer Cell ◽  
Antimicrobial Agents ◽  
Klebsiella Oxytoca ◽  
Cancer Cell Lines ◽  
Hybrid Compounds ◽  
Microbial Infections

Aim: To prepare a class of oleanolic-based compounds. Background: Conventional drugs used to treat infectious diseases suffer from limitations such as drug toxicity and drug resistance. The resistance of microbes to antimicrobial agents is a significant challenge in treating microbial infections. Combining two or more drugs with different modes of action to treat microbial infections results in a delay in developing drug resistance by the microbes. However, it is challenging to select the appropriate choice of drugs for combination therapy due to the differences in stability and pharmacokinetic profile of the drugs.Therefore, developing hybrid compounds using the existing drugs is a promising approach to design effective antimicrobial agents. Objectives: To prepare oleanolic-based hybrid compounds followed by characterization, in vitro antibacterial, and cytotoxicity evaluation. Methods:: Oleanolic acid-4-aminoquinoline-based hybrid compounds weresynthesized via esterification and amidation. The compounds werecharacterized using FTIR, NMR, and UHPLC-HRMS. Oleanolic acid was isolated from the flower buds of Syszygium aromaticum (L.) Merr. &.Perry, a specie from Kingdom Plantae, order Mytales in Myrtaceae family. Their antibacterial and cytotoxicity activity was determined against selected strains of bacteria assessed using the microdilution assay and sulforhodamine B assay against selected cancer cell lines. Results: The synthesized hybrid compounds exhibited significant antibacterial activity against the Gram-positive bacteria Enterococcus faecalis (ATCC13047), Bacillus subtilis (ATCC19659), Staphylococcus aureus as well as Gram-negative bacteria,Klebsiella oxytoca (ATCC8724), Escherischia coli (ATCC25922), and Proteus vulgaris (ATCC6380)with minimum inhibitory concentrations of 1.25 mg/mLcompared to oleanolic acid (2.5 mg/mL). Compounds 13 and 14 displayed significant cytotoxic effectsin vitro against the cancer cell lines (MCF-7 and DU 145) compared to the oleanolic acid (IC50 ˃ 200 µM). Conclusion: The present study revealed that the modification of C28 of OA enhanced its biological properties.

Anti-Cancer and Kinases Inhibitor Activities of Synthesized Heterocyclic Substituted Thiophene Fused with Cyclohexane Derivatives

2017 ◽  
Vol 14 (1) ◽  
pp. 768-774 ◽  
Author(s):  
Abd El-Galil E Amr ◽  
Hassan Z Ghanem ◽  
Mohamed A Al-Omar ◽  
Mohamed M Abdalla ◽  
Mohamed G Assy ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Mechanism Of Action ◽  
Sphingosine Kinase ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Kinase Inhibition ◽  
Wide Range ◽  
Anti Cancer

We herein report the anti-cancer and kinases inhibitor activities of some synthesized heterocyclic substituted thiophene fused with cyclohexane derivatives (Fig. 1) were synthesized before. Sixteen of these compounds were conveniently screened for their in vitro cytotoxicity against a wide range of cell lines, and showed potent activities against lung and leukemic cancer cell lines. The in vivo antilung and antileukemic cancers of the most active in vitro compounds was estimated and founded highly potent and compared to the standard drugs Bevacizumab and Etoposide. In search for the mechanism of action of anticancer activities it was found that these compounds exert its action via sphingosine kinase inhibition and inhibition of p53 ubiquitination.

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