Design, Synthesis, and Biological Evaluation of Camptothecin Loaded Biotinylated Cellulose Nanowhiskers as Anticancer Agents

Objective: Using biotinylated cellulose nanowhiskers (CNWs), we designed and synthesized a Glutathione (GSH) sensitive- Camptothecin (CPT) prodrug for selective CPT delivery (compound 12). Methods: CPT-biotin (compound 9), was synthesized by direct conjugation of CPT to the biotin via GSH sensitive linkage to evaluate the role of CNWs in compound 12. The chemical structures of the synthesized prodrugs were confirmed by FT-IR, 1H NMR, 13C NMR, and ESI-MS, while the nanoparticles were characterized by DLS and TEM. Results: The in-vitro drug release assay demonstrated that only 18.6% of CPT was released from the nano conjugate under GSH stimulation at micromolar level (100 μM), while 83.1% accumulative release rate was achieved under GSH stimulation at millimolar level (10 mM). The in-vitro cytotoxicity assay (MTT assay) demonstrated that compound 9showed higher inhibition ratios on biotin positive cells, MCF-7, and HepG2, and lower cytotoxicity on biotin negative, CHO. Compound 12 showed good activity against MCF-7, HepG2, and much lower cytotoxicity on CHO. Conclusion: This work demonstrates CPT-biotinylated cellulose nanowhiskers for selective chemotherapy and may have the potential to be used for cancer targeting.

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INDOLE DERIVATIVES: DESIGN, SYNTHESIS, IN-VITRO BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY AS ANTICANCER AGENTS

Kongunadu Research Journal ◽

10.26524/krj248 ◽

2018 ◽

Vol 5 (1) ◽

pp. 28-32

Author(s):

Amuthavalli A ◽

Prakash B ◽

Velmurugan R

Keyword(s):

Molecular Docking ◽

Anticancer Agents ◽

Docking Study ◽

Docking Studies ◽

Biological Evaluation ◽

In Vitro Cytotoxicity ◽

Molecular Docking Study ◽

Design Synthesis ◽

Standard Drug

New hetero annulated indoles were synthesized and structurally characterized by spectral means. In order to understand the nature of interactions of these molecules, we carried out molecular docking studies using the protein kinase CK2 inhibitors. The docking results provided some useful information for the futuredesign of more potent inhibitors. The in vitro cytotoxicity was evaluated for all the new compounds by MTT assay against HeLa and compared with the standard drug ellipticine. All the compounds showed moderate to potent activity against the cell lines. The preliminary structure–activity relationships were carried out.

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Hybridized Quinoline Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and Molecular Docking

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666181112121058 ◽

2019 ◽

Vol 19 (4) ◽

pp. 439-452 ◽

Cited By ~ 3

Author(s):

Mohamed R. Selim ◽

Medhat A. Zahran ◽

Amany Belal ◽

Moustafa S. Abusaif ◽

Said A. Shedid ◽

...

Keyword(s):

Cell Cycle ◽

Anticancer Agents ◽

Caspase 3 ◽

Biological Evaluation ◽

Tubulin Polymerization ◽

Design Synthesis ◽

Chemical Structures ◽

M Phase ◽

Induced Apoptosis ◽

Derivatives Of

Objective: Conjugating quinolones with different bioactive pharmacophores to obtain potent anticancer active agents. Methods: Fused pyrazolopyrimidoquinolines 3a-d, Schiff bases 5, 6a-e, two hybridized systems: pyrazolochromenquinoline 7 and pyrazolothiazolidinquinoline 8, different substituted thiazoloquinolines 13-15 and thiazolo[3,2-a]pyridine derivatives 16a-c were synthesized. Their chemical structures were characterized through spectral and elemental analysis, cytotoxic activity on five cancer cell lines, caspase-3 activation, tubulin polymerization inhibition and cell cycle analysis were evaluated. Results: Four compounds 3b, 3d, 8 and 13 showed potent activity than doxorubicin on HCT116 and three compounds 3b, 3d and 8 on HEPG2. These promising derivatives showed increase in the level of caspase-3. The trifloromethylphenyl derivatives of pyrazolopyrimidoquinolines 3b and 3d showed considerable tubulin polymerization inhibitory activity. Both compounds arrested cell cycle at G2/M phase and induced apoptosis. Conclusion: Compounds 3b and 3d can be considered as promising anticancer active agents with 70% of colchicine activity on tubulin polymerization inhibition and represent hopeful leads that deserve further investigation and optimization.

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Design, Synthesis and Biological Evaluation of Novel Benzothiazole Based [1,2,4]Triazolo[4,3-c]quinazoline Derivatives

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22453 ◽

2020 ◽

Vol 32 (3) ◽

pp. 580-586

Author(s):

Ranjit V. Gadhave ◽

Bhanudas S. Kuchekar

Keyword(s):

Biological Evaluation ◽

Bacterial Strains ◽

Active Compounds ◽

Design Synthesis ◽

Structural Modifications ◽

E Coli ◽

Chemical Structures ◽

Ft Ir ◽

Antioxidant Agent

A new series of N-(benzo[d]thiazol-2-yl)-[1,2,4]triazolo[4,3-c]quinazoline-5-carboxamide derivatives were synthesized by condensation of [1,2,4]triazolo[4,3-c]quinazoline-5-carboxylate derivatives with substituted benzothiazoles. The chemical structures of the synthesized compounds were confirmed by FT-IR, MS and 1H NMR spectra. Designed triazoloquinazoline derivatives were docked with oxido-reductase enzyme (PDB Code 4h1j) and DNA gyrase enzyme (PDB Code 3g75). Based on high binding affinity score, the best compound were selected for synthesis and subjected to in vitro antioxidant and antibacterial activity. Compounds 7a and 7d were found to be most active compounds as antioxidant agent among this series when compared with ascorbic acid. Compounds 7a, 7d and 7f were found to be most active compounds as an antibacterial agents among this series when compared with ciprofloxacin against bacterial strains such as S. aureus (ATCC 25923), E. coli (ATCC 25922) and P. aeruginosa (ATCC 27853). Study revealed that the most active compounds after structural modifications can be exploited as lead molecules for other pharmacological activities such as anti-inflammatory, anticancer and antidepressant activities.

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Synthesis and Biological Evaluation of Novel Triple-Modified Colchicine Derivatives as Potent Tubulin-Targeting Anticancer Agents

Cells ◽

10.3390/cells7110216 ◽

2018 ◽

Vol 7 (11) ◽

pp. 216 ◽

Cited By ~ 8

Author(s):

Urszula Majcher ◽

Greta Klejborowska ◽

Magdalena Kaik ◽

Ewa Maj ◽

Joanna Wietrzyk ◽

...

Keyword(s):

Cell Lines ◽

Anticancer Agents ◽

Binding Free Energy ◽

3D Structure ◽

Human Tumor ◽

Biological Evaluation ◽

Energy Estimates ◽

Colchicine Derivatives ◽

Mcf 7

Specific modifications of colchicine followed by synthesis of its analogues have been tested in vitro with the objective of lowering colchicine toxicity. Our previous studies have clearly shown the anticancer potential of double-modified colchicine derivatives in C-7 and C-10 positions. Here, a series of novel triple-modified colchicine derivatives is reported. They have been obtained following a four-step strategy. In vitro cytotoxicity of these compounds has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo, and LoVo/DX). Additionally, the mode of binding of the synthesized compounds was evaluated in silico using molecular docking to a 3D structure of β-tubulin based on crystallographic data from the Protein Data Bank and homology methodology. Binding free energy estimates, binding poses, and MlogP values of the compounds were obtained. All triple-modified colchicine derivatives were shown to be active at nanomolar concentrations against three of the investigated cancer cell lines (A549, MCF-7, LoVo). Four of them also showed higher potency against tumor cells over normal cells as confirmed by their high selectivity index values. A vast majority of the synthesized derivatives exhibited several times higher cytotoxicity than colchicine, doxorubicin, and cisplatin.

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Design, Synthesis, and Biological Evaluation of Pyridineamide Derivatives Containing a 1,2,3-Triazole Fragment as Type II c-Met Inhibitors

Molecules ◽

10.3390/molecules25010010 ◽

2019 ◽

Vol 25 (1) ◽

pp. 10 ◽

Cited By ~ 1

Author(s):

Hehua Xiong ◽

Jianxin Cheng ◽

Jianqing Zhang ◽

Qian Zhang ◽

Zhen Xiao ◽

...

Keyword(s):

Antitumor Activity ◽

Cell Lines ◽

Inhibitory Activity ◽

Docking Simulation ◽

Binding Mode ◽

Biological Evaluation ◽

Design Synthesis ◽

Ic50 Values ◽

Mcf 7

A series of 4-(pyridin-4-yloxy)benzamide derivatives containing a 1,2,3-triazole fragment were designed, synthesized, and their inhibitory activity against A549, HeLa, and MCF-7 cancer cell lines was evaluated. Most compounds exhibited moderate to potent antitumor activity against the three cell lines. Among them, the promising compound B26 showed stronger inhibitory activity than Golvatinib, with IC50 values of 3.22, 4.33, and 5.82 μM against A549, HeLa, and MCF-7 cell lines, respectively. The structure–activity relationships (SARs) demonstrated that the modification of the terminal benzene ring with a single electron-withdrawing substituent (fluorine atom) and the introduction of a pyridine amide chain with a strong hydrophilic group (morpholine) to the hinge region greatly improved the antitumor activity. Meanwhile, the optimal compound B26 showed potent biological activity in some pharmacological experiments in vitro, such as cell morphology study, dose-dependent test, kinase activity assay, and cell cycle experiment. Finally, the molecular docking simulation was performed to further explore the binding mode of compound B26 with c-Met.

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Design, Synthesis, Molecular Docking, ADME and Biological Evaluation Studies of Some New 1,3,4-oxadiazole Linked Benzimidazoles as Anticancer Agents and Aromatase Inhibitors

10.21203/rs.3.rs-975581/v1 ◽

2021 ◽

Author(s):

ulviye acar çevik ◽

Ismail Celik ◽

Ayşen IŞIK ◽

Yusuf Özkay ◽

Zafer Asım Kaplancıklı

Keyword(s):

Molecular Docking ◽

Cell Line ◽

Cell Lines ◽

Anticancer Agents ◽

Evaluation Studies ◽

Biological Evaluation ◽

Binding Modes ◽

Anticancer Activities ◽

Mcf 7

Abstract In this study, due to the potential anticancer effects of the benzimidazole ring system, a series of benzimidazole-1,3,4-oxadiazole derivatives were synthesized and characterized by 1H NMR, 13C NMR, and MS spectra analyses. In the in vitro anticancer assay, all the compounds tested anticancer activities using MTT-based assay against five cancer cell lines (MCF-7, A549, HeLa, C6, and HepG2). Among them, compound 5a exhibited the most potent activity with IC50 values of 5,165±0,211 μM and 5,995±0,264 μM against MCF-7 and HepG2 cell lines. Compound 5a was included in the BrdU test to determine the DNA synthesis inhibition effects for both cell types. Furthermore, compound 5c was also found to be more effective than doxorubicin on the HeLa cell line. The selectivity of anticancer activity was evaluated in NIH3T3 (mouse embryo fibroblast cell line) cell line. In vitro, enzymatic inhibition assays of aromatase enzyme were performed for compound 5a acting on the MCF-7 cell line. For compound 5a, in silico molecular docking against aromatase enzyme was performed to determine possible protein-ligand interactions and binding modes.

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Design, synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl)isatin derivatives as anticancer agents

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2013.12.001 ◽

2014 ◽

Vol 24 (2) ◽

pp. 591-594 ◽

Cited By ~ 28

Author(s):

Kailin Han ◽

Yao Zhou ◽

Fengxi Liu ◽

Qiannan Guo ◽

Pengfei Wang ◽

...

Keyword(s):

Anticancer Agents ◽

In Vitro Cytotoxicity ◽

Design Synthesis ◽

Isatin Derivatives

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Design, Synthesis and Potential Anti-Proliferative Activity of Some Novel 4-Aminoquinoline Derivatives

Acta Pharmaceutica ◽

10.2478/acph-2014-0030 ◽

2014 ◽

Vol 64 (3) ◽

pp. 285-297 ◽

Cited By ~ 3

Author(s):

Mostafa M. Ghorab ◽

Mansour S. Al-Said ◽

Reem K. Arafa

Keyword(s):

Anticancer Agents ◽

Proliferative Activity ◽

Cancer Cell Line ◽

The Novel ◽

Design Synthesis ◽

Reference Drug ◽

Antiproliferative Agents ◽

New Compounds ◽

Mcf 7

Abstract Novel nineteen compounds based on a 4-aminoquinoline scaffold were designed and synthesized as potential antiproliferative agents. The new compounds were N-substituted at the 4-position by aryl or heteroaryl (1-9), quinolin- 3-yl (10), 2-methylquinolin-3-yl (11), thiazol-2-yl (12), and dapsone moieties (13, 14 and 18). Bis-compounds 15, 16 and 19 were also synthesized to assess their biological activity. All the newly synthesized comounds were tested for in vitro antiproliferative activity against the MCF-7 breast cancer cell line. Seventeen of the novel compounds showed higher activity than the reference drug doxorubicin. The corresponding 7-(trifluoromethyl)-N-(3,4,5-trimethoxyphenyl)quinolin-4- amine 1, N-(7-(trifluoromethyl)quinolin-4-yl)quinolin- 3- amine (10), 2-methyl-N-(7-trifluorome-thyl)quinolin-4-yl) quinolin-3-amine (11) and N-(4-(4-aminophenylsulfonyl) phenyl)-7-chloroquinolin-4-amine (13) were almost twice to thrice as potent as doxorubicin. Biological screening of the tested compounds could offer an encouraging framework in this field that may lead to the discovery of potent anticancer agents.

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Design, Synthesis and In-Vitro Biological Evaluation of Antofine and Tylophorine Prodrugs as Hypoxia-Targeted Anticancer Agents

Molecules ◽

10.3390/molecules26113327 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3327

Author(s):

Ziad Omran ◽

Chris P. Guise ◽

Linwei Chen ◽

Cyril Rauch ◽

Ashraf N. Abdalla ◽

...

Keyword(s):

Anticancer Agents ◽

Biological Activities ◽

Multidrug Resistant ◽

Biological Evaluation ◽

High Chemical ◽

Design Synthesis ◽

Hypoxic Conditions ◽

Cancerous Cell

Phenanthroindolizidines, such as antofine and tylophorine, are a family of natural alkaloids isolated from different species of Asclepiadaceas. They are characterized by interesting biological activities, such as pronounced cytotoxicity against different human cancerous cell lines, including multidrug-resistant examples. Nonetheless, these derivatives are associated with severe neurotoxicity and loss of in vivo activity due to the highly lipophilic nature of the alkaloids. Here, we describe the development of highly polar prodrugs of antofine and tylophorine as hypoxia-targeted prodrugs. The developed quaternary ammonium salts of phenanthroindolizidines showed high chemical and metabolic stability and are predicted to have no penetration through the blood–brain barrier. The designed prodrugs displayed decreased cytotoxicity when tested under normoxic conditions. However, their cytotoxic activity considerably increased when tested under hypoxic conditions.

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Design, Synthesis of novel coumarin conjugated acetamides as promising anticancer agents: An in-silico and in-vitro approach.

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200714140820 ◽

2020 ◽

Vol 20 ◽

Author(s):

Mamatha S. V ◽

S. L. Belagali ◽

Mahesh Bhat ◽

Vijay M. Kumbar

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Mtt Assay ◽

Anticancer Agents ◽

In Silico ◽

Active Sites ◽

Biological Activities ◽

Biological Evaluation ◽

Mcf 7

Background: Coumarin and benzophenone possess a vast sphere of biological activities whereas thiazoles display various pharmacological properties. Hence we focused on incorporation of coumarin and thiazole core to the benzophenone skeleton to enhance the bioactivity anticipating their interesting biological properties. Objective: The objective of the current work is synthesis and biological evaluation of a novel series of coumarin fused thiazole derivatives. Methods: A novel series of Coumarin conjugated thiazolyl acetamide hybrid derivatives were synthesized by multistep reaction sequence and were characterized by the FT-IR, LCMS and NMR spectral techniques. The newly synthesized compounds were screened for anticancer activity by in-silico and in-vitro methods. The cytotoxicity of the synthesized unique compounds had been executed for two different cancer cell lines MCF-7 (Breast cancer) and KB (Oral cancer) in comparison with standard paclitaxel by MTT assay. Results: The compound 7f is the potent motif with an acceptable range of IC 50 values for anticancer activity were 63.54 µg/ml and 55.67 µg/ml, against the MCF-7 and KB cell lines, respectively. Molecule docking model revealed that this compound formed three conventional hydrogen bonds with the active sites of the amino acids MET 769, ARG 817 and LYS 721. Conclusion: Compound 7f with two methyl groups on the phenoxy ring and one 4-position methoxy group on the benzoyl ring, showed a significant cytotoxic effect. An advantageous level of low toxicity against normal cell line (L292) by MTT assay was determined.

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