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 PVA coating of ferrite nanoparticles triggers pH-responsive release of 5-fluorouracil in cancer cells

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sanele Mngadi ◽  
Moganavelli Singh ◽  
Seipati Mokhosi
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Targeted Delivery ◽  
Colloidal Stability ◽  
Therapeutic Potential ◽  
Cancer Cell Lines ◽  
Ferrite Nanoparticles ◽  
Cancer Drug ◽  
Anti Cancer

Abstract The use of magnetic nanoparticles (MNPs) has transformed both diagnostics and therapeutic approaches in cancer treatment. Along with developing novel anti-cancer drugs with high therapeutic potential, researchers are exploring innovative strategies for more targeted delivery in order to alleviate the associated potent side effects. In this study, we describe the synthesis of Mg0.5Co0.5Fe2O4 ferrite nanoparticles, their functionalisation with polyvinyl alcohol (PVA), and encapsulation of the anti-cancer drug 5-fluorouracil (5-FU). Functionalised nanoparticles viz. PVA-Mg0.5Co0.5Fe2O4 -5-FU displayed desirable physiochemical properties with regards to the spherical shape, hydrodynamic sizes of <120 nm and relative colloidal stability of up to <−33 mV. The drug encapsulating efficiency was found to be 68%. In vitro cytotoxicity profiles were determined using the MTT and SRB assays, with >65% cell death recorded in MCF-7 and HeLa cancer cell lines. Overall, the nanocomposites exhibited excellent physiochemical elements, high specificity towards cancerous cells and displayed pH-sensitive drug release in a simulated acidic tumour micro-environment. The encapsulation of 5-FU improved bioavailability of the drug in cancer cell lines for a prolonged duration, with the promise to enhance its therapeutic effect, biocompatibility and safety. These MNPs present as promising in vitro delivery systems that can further developed for therapeutic applications.

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 Implementation of the NCI-60 Human Tumor Cell Line Panel to Screen 2260 Cancer Drug Combinations to Generate >3 Million Data Points Used to Populate a Large Matrix of Anti-Neoplastic Agent Combinations (ALMANAC) Database

2018 ◽  
Vol 24 (3) ◽  
pp. 242-263 ◽  
Author(s):  
David A. Close ◽  
Allen Xinwei Wang ◽  
Stanton J. Kochanek ◽  
Tongying Shun ◽  
Julie L. Eiseman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Growth Inhibition ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Large Matrix ◽  
Data Points

Animal and clinical studies demonstrate that cancer drug combinations (DCs) are more effective than single agents. However, it is difficult to predict which DCs will be more efficacious than individual drugs. Systematic DC high-throughput screening (HTS) of 100 approved drugs in the National Cancer Institute’s panel of 60 cancer cell lines (NCI-60) produced data to help select DCs for further consideration. We miniaturized growth inhibition assays into 384-well format, increased the fetal bovine serum amount to 10%, lengthened compound exposure to 72 h, and used a homogeneous detection reagent. We determined the growth inhibition 50% values of individual drugs across 60 cell lines, selected drug concentrations for 4 × 4 DC matrices (DCMs), created DCM master and replica daughter plate sets, implemented the HTS, quality control reviewed the data, and analyzed the results. A total of 2620 DCMs were screened in 60 cancer cell lines to generate 3.04 million data points for the NCI ALMANAC (A Large Matrix of Anti-Neoplastic Agent Combinations) database. We confirmed in vitro a synergistic drug interaction flagged in the DC HTS between the vinca-alkaloid microtubule assembly inhibitor vinorelbine (Navelbine) tartrate and the epidermal growth factor-receptor tyrosine kinase inhibitor gefitinib (Iressa) in the SK-MEL-5 melanoma cell line. Seventy-five percent of the DCs examined in the screen are not currently in the clinical trials database. Selected synergistic drug interactions flagged in the DC HTS described herein were subsequently confirmed by the NCI in vitro, evaluated mechanistically, and were shown to have greater than single-agent efficacy in mouse xenograft human cancer models. Enrollment is open for two clinical trials for DCs that were identified in the DC HTS. The NCI ALMANAC database therefore constitutes a valuable resource for selecting promising DCs for confirmation, mechanistic studies, and clinical translation.

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.

Lead Generation for Human Mitotic Kinesin Eg5 using Structure-based Virtual Screening and Validation by in vitro and Cell-based Assays

2020 ◽  
Vol 16 ◽  
Author(s):  
Himesh Makala ◽  
Soundarya Priya Alexandar ◽  
Devipriya Nagarajan ◽  
Santanu Kar Mahapatra ◽  
Venkatasubramanian Ulaganathan
Keyword(s):  
Virtual Screening ◽  
Cell Lines ◽  
Cancer Cell ◽  
Mitotic Cell ◽  
Cancer Cell Lines ◽  
Allosteric Site ◽  
Drug Candidates ◽  
Kinesin Eg5 ◽  
Mitotic Kinesin Eg5

Background: Human mitotic kinesins play a crucial role in mitotic cell division. Targeting the spindle separation phase of mitosis has gained much attention pharmaceutically in cancer chemotherapy. Spindle segregation is carried out mainly by Eg5 kinesin, and currently, it has many inhibitors in different phases of clinical trials. All the current drug candidates bind un-competitively with ATP/ADP at allosteric site 1 (formed by loop L5, helix α2 and helix α3). Recent experiments show that inhibitors that bind to the site 2 (formed by helix α4 and helix α6) are either competitive or uncompetitive to ATP/ADP. Objectives: To identify suitable lead compounds that target the mitotic kinesin Eg5, using in silico screening and their validation using in vitro and cell-based assays. Methodology: We have screened for potential inhibitors for human Eg5 (kinesin-5) through structure-based virtual screening and validated the top-scoring compounds using steady-state ATPase assay, differential scanning fluorimetry and microscale thermophoresis. The anticancer activity of the compounds was evaluated in the epithelial (A549) and chronic myelogenous leukaemia (K562) cancer cell lines. A known strong binding inhibitor S-trityl-L-cystine is used as a reference compound. Results & Conclusion: Of the many compounds tested, MM01 and MM03 showed good cell-based activity against the cancer cell lines A549 and K562 and can be further studied in animal models.

scholarly journals Synthesis and Bioactivity of Thiosemicarbazones Containing Adamantane Skeletons

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 324 ◽  
Author(s):  
Van Hien Pham ◽  
Thi Phuong Dung Phan ◽  
Dinh Chau Phan ◽  
Binh Duong Vu
Keyword(s):  
Candida Albicans ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Inhibitory Effect ◽  
Hydroxyl Groups ◽  
Gram Negative Bacteria ◽  
Inhibitory Potency ◽  
Mcf 7

Reaction of 4-(1-adamantyl)-3-thiosemicarbazide (1) with numerous substituted acetophenones and benzaldehydes yielded the corresponding thiosemicarbazones containing adamantane skeletons. The synthesized compounds were evaluated for their in vitro activities against some Gram-positive and Gram-negative bacteria, and the fungus Candida albicans, and cytotoxicity against four cancer cell lines (Hep3B, HeLa, A549, and MCF-7). All of them showed good antifungal activity against Candida albicans. Compounds 2c, 2d, 2g, 2j and 3a, 3e, 3g displayed significant inhibitory activity against Enterococcus faecalis. Compounds 2a, 2e, 2h, 2k and 3j had moderate inhibitory potency against Staphylococcus aureus. Compounds 2a, 2e and 2g found so good inhibitory effect on Bacillus cereus. Compounds 2d and 2h, which contain (ortho) hydroxyl groups on the phenyl ring, were shown to be good candidates as potential agents for killing the tested cancer cell lines, i.e., Hep3B, A549, and MCF-7. Compounds 2a–c, 2f, 2g, 2j, 2k, 3g, and 3i were moderate inhibitors against MCF-7.

scholarly journals Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance

2011 ◽  
Vol 108 (46) ◽  
pp. 18708-18713 ◽  
Author(s):  
J.-P. Gillet ◽  
A. M. Calcagno ◽  
S. Varma ◽  
M. Marino ◽  
L. J. Green ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Cancer Drug Resistance ◽  
Anti Cancer

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.

Design, Synthesis and Biological Evaluation of 4, 6-Coumarin Derivatives as Anti-Cancer and Apoptosis-Inducing Agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Guoyi Yan ◽  
Jiang Luo ◽  
Xuan Han ◽  
Wenjuan Zhang ◽  
Chunlan Pu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Cancer Drug ◽  
Dependent Manner ◽  
Coumarin Derivatives ◽  
In Silico Admet ◽  
Anti Cancer ◽  
Synthesis And Biological Evaluation

BACKGROUND: : Coumarin structures were widely employed in anti-cancer drug design. Herein we focused on the modifications of C4 and C6 positions on coumarin scaffold to get novel anti-cancer agents. OBJECTIVE: The objective of the current work was the synthesis and biological evaluation of a series of 4, 6-coumarin derivatives to get novel anticancer agents. METHODS: Thirty-seven coumarin derivatives were designed and synthesized, the antiproliferative activity of the compounds were evaluated against human cancer cell lines and non-cancerous cells by MTT assay. The bioactivities and underling mechanisms of active molecules were studied and the ADMET characters were predicted. RESULTS: Among the compounds, 4-phydroxy phenol-6-pinacol borane coumarin (25) exhibited a promising anti-cancer activity to cancer cell lines in dose-dependent manner and the toxicity to normal cells was low. The mechanism of action was observed through inducing G2/M phase arrest and apoptosis which was further confirmed via western blot. In silico ADMET prediction revealed that compound 25 is a drug-like small molecule with a favorable safety profile. CONCLUSION: The findings in this work may give vital information for further development of 6-pinacol borane coumarin derivatives as novel anti-cancer agents.

Sign in / Sign up

Export Citation Format

Share Document