Tumoricidal Potential of Novel Amino-1,10-phenanthroline Derived Imine Ligands: Chemical Preparation, Structure, and Biological Investigations

Herein we report the synthesis and structural elucidation of two novel imine-based ligands, 2-(1,10-phenanthrolin-5-yl)imino)methyl)-5-bromophenol (PIB) and N-(1,10-phenanthrolin-5-yl)-1-(thiophen-3-yl)methanimine (PTM) ligands. An in vitro cytotoxicity assay of the synthesized molecules was carried out against breast, cervical, colorectal, and prostate cancer cell lines as well as immortalized human keratinocytes. The observations indicated that both the molecules possesses dose-dependent selective cytotoxicity of cancer cells with no detrimental effect on the normal cell lines. Furthermore, the detailed computational analysis of newly synthetized ligands (PIB and PTM) has been conducted in order to identify their most important parts from the perspective of local reactivity. The IC50 values of PIB treatment on MCF-7, HeLa, HCT-116 and PC-3 were 15.10, 16.25, 17.88, 17.55 and 23.86 micromoles, respectively. Meanwhile, the IC50 values of PTM on MCF-7, HeLa, HCT-116, PC-3 and HaCat were observed to be 14.82, 15.03, 17.88, 17.28 and 21.22 micromoles, respectively. For computational analysis, we have employed the combination of Density Functional Theory (DFT) calculations and MD simulations. DFT calculations provided us with information about structure and reactivity descriptors based on the electron distribution. Surfaces of molecular electrostatic potential (MEP) and averaged local ionization energy (ALIE) indicated the sites within studied molecules that are most reactive. These results indicated the importance of nitrogen atoms and OH group. Additionally, the values of bond dissociation for hydrogen abstraction showed that both molecules, especially the PTM, are stable toward the influence of autoxidation mechanism. On the other side, MD simulations gave us an insight how ligands interact with water molecules. Namely, the radial distribution functions (RDF) indicated that the hydrogen atom of the OH group in the case of the PIB has the most pronounced interactions with water.

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Design, Synthesis, Antibacterial, Antifungal and Anticancer Evaluations of Novel β-Pinene Quaternary Ammonium Salts

International Journal of Molecular Sciences ◽

10.3390/ijms222011299 ◽

2021 ◽

Vol 22 (20) ◽

pp. 11299

Author(s):

Li Zhang ◽

Xue-Zhen Feng ◽

Zhuan-Quan Xiao ◽

Guo-Rong Fan ◽

Shang-Xing Chen ◽

...

Keyword(s):

Cell Lines ◽

Anticancer Agents ◽

Quaternary Ammonium ◽

Biological Activities ◽

Cell Membrane Permeability ◽

Vitro Assay ◽

Ic50 Values ◽

Hct 116 ◽

Mcf 7

β-pinene is a monoterpene isolated from turpentine oil and numerous other plants’ essential oils, which has a broad spectrum of biological activities. In the current work, six novel β-pinene quaternary ammonium (β-PQA) salts were synthesized and evaluated in vitro for their antifungal, antibacterial and anticancer activities. The in vitro assay results revealed that compounds 4a and 4b presented remarkable antimicrobial activity against the tested fungi and bacteria. In particular, compound 4a showed excellent activities against F. oxysporum f.sp. niveum, P. nicotianae var.nicotianae, R. solani, D. pinea and Fusicoccumaesculi, with EC50 values of 4.50, 10.92, 9.45, 10.82 and 6.34 μg/mL, respectively. Moreover, compound 4a showed the best antibacterial action against E. coli, P. aeruginosa, S. aureus and B. subtilis, with MIC at 2.5, 0.625, 1.25 and 1.25 μg/mL, respectively. The anticancer activity results demonstrated that compounds 4a, 4b, 4c and 4f exhibited remarkable activity against HCT-116 and MCF-7 cell lines, with IC50 values ranged from 1.10 to 25.54 μM. Notably, the compound 4c displayed the strongest cytotoxicity against HCT-116 and MCF-7 cell lines, with the IC50 values of 1.10 and 2.46 μM, respectively. Furthermore, preliminary antimicrobial mechanistic studies revealed that compound 4a might cause mycelium abnormalities of microbial, cell membrane permeability changes and inhibition of the activity of ATP. Altogether, these findings open interesting perspectives to the application of β-PQA salts as a novel leading structure for the development of effective antimicrobial and anticancer agents.

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Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

Molecules ◽

10.3390/molecules26133923 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3923

Author(s):

Adel A.-H. Abdel-Rahman ◽

Amira K. F. Shaban ◽

Ibrahim F. Nassar ◽

Dina S. EL-Kady ◽

Nasser S. M. Ismail ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Molecular Docking Study ◽

Human Cancer Cell Lines ◽

Hct 116 ◽

Mcf 7

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

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In vitro Screening of Berberis lycium Root Extract on HCT-116 and MCF-7 Cell Lines

10.36468/pharmaceutical-sciences.spl.11 ◽

2020 ◽

Vol 20 (s2) ◽

Author(s):

Xiaolin Hu ◽

S. Islam ◽

Fuad Ameen ◽

Abdullah A. Alarfaj ◽

G. Murtaza ◽

...

Keyword(s):

Cell Lines ◽

Root Extract ◽

In Vitro Screening ◽

Hct 116 ◽

Berberis Lycium ◽

Mcf 7

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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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Synthesis, Anticancer Activity, and Molecular Modeling of New Halogenated Spiro[pyrrolidine-thiazolo-oxindoles] Derivatives

Applied Sciences ◽

10.3390/app10062170 ◽

2020 ◽

Vol 10 (6) ◽

pp. 2170 ◽

Cited By ~ 3

Author(s):

Mohammad Shahidul Islam ◽

Abdullah Mohammed Al-Majid ◽

Fardous F. El-Senduny ◽

Farid A. Badria ◽

A. F. M. Motiur Rahman ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Single Step ◽

One Pot ◽

Antiproliferative Effects ◽

Physiochemical Parameters ◽

Hct 116 ◽

Mcf 7

A one-pot, single-step, and an atom-economical process towards the synthesis of highly functionalized spirooxindoles analogues was efficiently conducted to produce a satisfactory chemical yields (70–93%) with excellent relative diastereo-, and regio-selectivity. An in vitro antiproliferative assay was carried out on different cancer cell lines to evaluate the biological activity of the synthesized tetrahydro-1’H-spiro[indoline-3,5’-pyrrolo[1,2-c]thiazol]-2-one 5a–n. The prepared hybrids were then tested in vitro for their antiproliferative effects against three cancer cell lines, namely, HepG2 (liver cancer), MCF-7 (breast cancer), and HCT-116 (colon cancer). The spirooxindole analogue 5g exhibited a broad activity against HepG2, MCF-7, and HCT-116 cell lines of liver, breast, and colorectal cancers when compared to cisplatin. Modeling studies including shape similarity, lipophilicity scores, and physicochemical parameters were calculated. The results of this study indicated that spirooxindole analogue 5g retained a good physiochemical parameters with acceptable lipophilicity scores.

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Synthesis of new 3-(substituted-phenyl)-N-(2-hydroxy-2-(substituted-phenyl)ethyl)-N-methylthiophene-2-sulfonamide derivatives as antiproliferative agents

European Journal of Chemistry ◽

10.5155/eurjchem.9.1.13-21.1669 ◽

2018 ◽

Vol 9 (1) ◽

pp. 13-21 ◽

Cited By ~ 3

Author(s):

Chandrakant Pawar ◽

Dattatraya Pansare ◽

Devanand Shinde

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

1H Nmr ◽

13C Nmr ◽

Antiproliferative Activity ◽

Positive Control ◽

Antiproliferative Agents ◽

Ic50 Values ◽

Mcf 7

In the present work, we report the synthesis of a series of 3-(substituted phenyl)-N-(2-hydroxy-2-(substituted-phenyl)ethyl)-N-methylthiophene-2-sulfonamide derivatives through Suzuki and Buchwald reaction. We have optimized methodology for targets from milligram to multi-gram scale. The newly synthesized compounds were characterized by 1H NMR, 19F NMR, 13C NMR, LC-MS techniques and purity was further checked by HPLC. The compounds were evaluated for their in-vitro antiproliferative activity against MCF-7, HeLa, A-549 and Du-145 cancer cell lines by CCK-8 assay. The preliminary bioassay suggests that most of the compounds show antiproliferation with different degrees and 5-fluorouracil was used as positive control. Among these compounds 2d, 2g, 2i, 4e, 4h and 4k are most active compared to the standard. All the synthesized compounds show IC50 values from 1.82-9.52 µM in different cell lines. Amongst these, compounds 2d, 2g, 2i, 4e, 4h and 4k were most potent, with IC50 values ranging from 1.82-4.28 µM in different cell lines.

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Evaluating the Anticancer Potentials of Methanol Extracted Annona muricata Fruit Pulp and Seed(s) Phytochemicals

Clinical Oncology and Research ◽

10.31487/j.cor.2020.08.04 ◽

2020 ◽

pp. 1-8

Author(s):

D. Devananda ◽

Shashanka K Prasad ◽

D. Devananda

Keyword(s):

Traditional Medicine ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Antioxidant Activities ◽

Annona Muricata ◽

Fruit Pulp ◽

Hct 116 ◽

Mcf 7

Annona muricata L. has been widely used in traditional medicine for the treatment of various diseases ranging from fever to cancer. In this study, we evaluate the in vitro anticancer potential of methanol extracted A. muricata fruit pulp (AMPM) and seeds (AMSM) phytochemicals against breast (MCF-7), cervical (HeLa), prostate (PC-3) and colorectal (HCT-116) cancer cell lines. Additionally, the in vitro antiinflammatory and antioxidant activities of the extracts have been carried. The findings suggest that the AMSM is the most potent among the either extracts. Notwithstanding, both AMPM and AMSM showed significant dose and cell line-dependent anticancer potential(s).

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Two New Cytotoxic Steroidal Alkaloids from Sarcococca Hookeriana

Molecules ◽

10.3390/molecules24010011 ◽

2018 ◽

Vol 24 (1) ◽

pp. 11 ◽

Cited By ~ 1

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.

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IN-VITRO CYTOTOXICITY AND ANTIOXIDANT EVALUATION OF 7-AMINO-2-STYRYLCHROMONE DERIVATIVES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i11.20587 ◽

2017 ◽

Vol 10 (11) ◽

pp. 152

Author(s):

Lalitha Simon

Keyword(s):

Nitric Oxide ◽

Cell Lines ◽

Aromatic Aldehydes ◽

In Vitro Cytotoxicity ◽

Hct 116 ◽

Dpph Scavenging Activity ◽

Diphenyl Tetrazolium Bromide ◽

Dpph Scavenging ◽

Mcf 7

Objective: The objective of this study was to synthesize 7-amino-2-styrylchromone derivatives and evaluate their in vitro cytotoxic and antioxidant potential.Methods: 7-amino-2-styrylchromones were synthesized from 7-amino-2-methylchromone by condensing it with various substituted aromatic aldehydes. The cytotoxicity of the synthesized molecules was assessed against two cell lines, MCF-7 and HCT-116 by 3-(4,5-dimethyl thiazol-2-yl)-2,5- diphenyl tetrazolium bromide assay. Cell cycle analysis of the most potent molecule ASC-7 was carried out. The antioxidant studies were conducted by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide methods.Result: (E)-7-amino-2-(3,4-methylenedioxystyryl)-4H-chromen-4-one (ASC-7) with inhibitory concentration 50% (IC50) 56.0 μM was found to be the most potent molecule against MCF-7. ASC-7 induced G0/G1 phase arrest of MCF-7. Furthermore, (E)-7-amino-2-(3,4-methylenedioxystyryl)- 4H-chromen-4-one(ASC-7) showed good DPPH scavenging activity (IC50 54.6 μM). However, none of the tested compounds exhibited nitric oxide scavenging property.Conclusion: This study reports the synthesis of 7-amino-2-styrylchromones. Some of the synthesized compounds showed moderate cytotoxicity against the tested cell lines MCF-7 and HCT-116. (E)-7-amino-2-(3,4-methylenedioxystyryl)-4H-chromen-4-one (ASC-7) was found to be the best cytotoxic and antioxidant agent.

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Cytotoxic Flavones from the Stem Bark of Bougainvillea spectabilis Willd

Planta Medica ◽

10.1055/s-0043-118102 ◽

2017 ◽

Vol 84 (02) ◽

pp. 129-134 ◽

Cited By ~ 3

Author(s):

Lien Do ◽

Thammarat Aree ◽

Pongpun Siripong ◽

Nga Vo ◽

Tuyet Nguyen ◽

...

Keyword(s):

Cell Lines ◽

Stem Bark ◽

In Vitro Cytotoxicity ◽

Crystallographic Analysis ◽

Ionization Mass ◽

Etoac Extract ◽

Ic50 Values ◽

Bougainvillea Spectabilis ◽

Mcf 7

AbstractFive new flavones possessing a fully substituted A-ring with C-6 and C-8 methyl groups, bougainvinones I – M (1–5), along with three known congeners, 2′-hydroxydemethoxymatteucinol (6), 5,7,3′,4′-tetrahydroxy-3-methoxy-6,8-dimethylflavone (7) and 5,7,4′-trihydroxy-3-methoxy-6,8-dimethylflavone (8), were isolated from the EtOAc extract of the stem bark of Bougainvillea spectabilis. Their structures were established by means of spectroscopic data (ultraviolet, infrared, high-resolution electrospray ionization mass spectrometry, and one-dimensional and two-dimensional nuclear magnetic resonance) and single-crystal X-ray crystallographic analysis. The in vitro cytotoxicity of all isolated compounds against five cancer cell lines (KB, HeLa S-3, MCF-7, HT-29, and HepG2) was evaluated. Compound 5 showed promising cytotoxic activity against the KB and HeLa S-3 cell lines, with IC50 values of 7.44 and 6.68 µM. The other compounds exhibited moderate cytotoxicity against the KB cell line.

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