One-Pot Synthesis of 5-(Het)Aryl 8-Aminoquinoline Amide Derivatives as Potential Antibacterial / Cytotoxic Agents

Background: The 8-Aminoquinoline (8-AQ) framework has attracted particular attention in the discovery and development of antimalarial and anti-bacterial agents or drugs. However, the clinical uses of 8-AQ based drugs are often associated with toxic side effects such as methemoglobinemia and hemolytic anemia with deficiency in Glucose-6-Phosphate Dehydrogenase (G6PD) Activity. The 4-aryl- 8-amino(acetamido)quinoline derivatives, on the other hand, have shown antiproliferative activities against cancer cell lines. These reports prompted us to assess the antibacterial and cytotoxic activities of a series of compounds based on 5-aryl 8-aminoquinoline amide scaffold. Methods: A series of compounds based on 5-(het)aryl 8-aminoquinoline amide scaffold was synthesized via a one-pot ultrasound-assisted method using a C-5 selective halogenation of quinoline derivatives followed by Pd/C-catalyzed Suzuki-Miyaura coupling with (het)aryl boronic acids. All these compounds were evaluated for their in vitro antibacterial activities against representative Gram-(+) and Gram-(-) strains including Escherichia coli, Pseudomonas aeruginosa, Klebsiella species and Staphylococcus aureus. Three compounds were further tested for cytotoxicities in vitro against breast adenocarcinoma (MCF7) and Hepatocellular Carcinoma (HepG2) along with non-cancerous human embryonic kidney (HEK293) cell lines. Results: All these compounds demonstrated moderate to good antibacterial activities against the four organisms used. In vitro assay results revealed that three compounds showed good activities against Gram-(+) strains and Gram-(-) strains and one was comparable to ciprofloxacin and pefloxacin. These three compounds were further tested for their cytotoxic properties against MCF7 and HepG2 cell lines. One of them showed IC50 value comparable to doxorubicin when tested against HepG2 cell lines. However, none of these compounds showed any significant effects when tested against HEK293 cells indicating their selectivity towards the growth inhibition of cancer cells. Conclusion: A series of compounds based on 5-(het)aryl 8-aminoquinoline amide scaffold was synthesized and evaluated for antibacterial and cytotoxic activities. Several of these compounds showed promising antibacterial and cytotoxic activities when tested in vitro suggesting that the present class of compounds may be of interest for the identification of new and potential antibacterial / cytotoxic agents.

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Green Synthesis of Silver Nanocomposites of Nigella sativa Seeds Extract for Hepatocellular Carcinoma

Current Nanomaterials ◽

10.2174/2468187309666190906130115 ◽

2019 ◽

Vol 4 (3) ◽

pp. 191-200 ◽

Cited By ~ 1

Author(s):

Afreen Usmani ◽

Anuradha Mishra ◽

Asif Jafri ◽

Md Arshad ◽

Mohd Aftab Siddiqui

Keyword(s):

Hepatocellular Carcinoma ◽

Green Synthesis ◽

Hepg2 Cell ◽

Cell Lines ◽

Nigella Sativa ◽

Uv Spectroscopy ◽

Silver Nanocomposites ◽

Natural Drugs ◽

Hepg2 Cell Lines

Background: Silver nanoparticles play a significant role in bioavailability and refining the compatibility of natural drugs in the treatment of various chronic diseases including different types of cancer. Objective: Green synthesis of silver nanocomposites of Nigella sativa seeds extract to evaluate the anticancer effects against hepatocellular carcinoma using HepG2 cell lines. Methods: The AgNCs were developed by treating aqueous extract of N. sativa seeds treated with silver nitrate (1mM) solution and were used to test its efficacy against hepatocellular carcinoma using HepG2 cell lines. Results and Discussion: The Surface Plasmon Resonance (SPR) of prepared AgNCs showed a peak at 432 nm via UV spectroscopy. The selected N. sativa AgNCs were characterized for polydispersity, surface charge and size and the results showed 0.215±0.093 polydispersity index (PDI), zeta potential 18.8±0.372 mV and size range 10-20 nm, respectively. The Fourier transform infrared spectroscopy (FTIR) also showed various peak of functional groups that are possibly involved in the reduction of silver ion and synthesized the N. sativa silver nanocomposites, respectively. N. sativa AgNCs showed 89.954% drug release while in the case of extract release, it was only 33.821% in 24 hrs. Further, in vitro studies of N. sativa AgNCs against hepatocellular carcinoma showed good cytotoxic effect p<0.05 with 7.16 µg/ml IC50 value. Conclusion: Thus, the present results revealed that green synthesis of N. sativa AgNCs can be an alternative tool for clinical application in cancer therapy; however, there is a need to find the mechanism and role of AgNCs inside the individual.

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Synthesis and In Silico Docking of New Pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine-based Cytotoxic Agents

International Journal of Molecular Sciences ◽

10.3390/ijms221910258 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10258

Author(s):

Mabrouk Horchani ◽

Niels V. Heise ◽

Sophie Hoenke ◽

René Csuk ◽

Abdel Halim Harrath ◽

...

Keyword(s):

Cell Lines ◽

Anticancer Agents ◽

In Silico ◽

Human Tumor ◽

In Vitro Cytotoxicity ◽

Cytotoxic Agents ◽

Hek293 Cells ◽

Binding Interaction ◽

In Silico Docking

To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine derivativeshave been designed and synthesized viacyclocondensation reactions of pyrazolo-enaminone with a series of arylidenemalononitriles; compound 5 was obtained from 5-amino-4-cyanopyrazole. The structures of the target compounds were investigated by spectral techniques and elemental analysis (IR, UV–Vis, 1H NMR, 13C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells. It has been found that the pyrazolo-pyrido-pyrimidine analog bearing a 4-Br-phenyl moiety was the most active toward many cell lines with EC50 values ranging between 9.1 and 13.5 µM. Moreover, in silico docking studies of the latter with six anticancer drug targets, i.e., DHFR, VEGFR2, HER-2/neu, hCA-IX, CDK6 and LOX5, were also performed, in order to gain some insights into their putative mode of binding interaction and to estimate the free binding energy of this bioactive molecule.

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Synthesis and In Silico Docking of New Pyrazolo[4,3-e]Pyrido[1,2-a]Pyrimidine-Based Cytotoxic Agents

10.20944/preprints202109.0188.v1 ◽

2021 ◽

Author(s):

Mabrouk Horchani ◽

Niels V. Heise ◽

Sophie Hoenke ◽

Rene Csuk ◽

Abdel Halim Harrath ◽

...

Keyword(s):

Cell Lines ◽

Anticancer Agents ◽

In Silico ◽

Human Tumor ◽

In Vitro Cytotoxicity ◽

Cytotoxic Agents ◽

Hek293 Cells ◽

Binding Interaction ◽

In Silico Docking

To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine derivatives 7a-l have been designed and synthesized via cyclocondensation reactions of pyrazolo-enaminone 5 with a series of arylidene malononitriles; compound 5 was obtained from 5-amino-4-cyanopyrazole (3). The structures of the target compounds 7a-l were investigated by spectral techniques and elemental analysis (IR, UV-Vis, 1H NMR, 13C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells. It has been found that the conjugate 7e was the most active towards many cell lines with EC50 values ranging between 9.1 and 13.5 µM, respectively. Moreover, in silico docking studies of 7e with six anticancer drug targets, i.e. DHFR, VEGFR2, HER-2/neu, hCA-IX, CDK6 and LOX also was performed, in order to gain some insights into their putative mode of binding interaction and to estimate the free binding energy of this bioactive molecule.

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Nano-SnCl4/SiO2 as a Catalyst for One-Pot Synthesis of Substituted 1H-Pyrazoles as Antifungal and Cytotoxic Agents

Letters in Organic Chemistry ◽

10.2174/1570178617666191127104622 ◽

2020 ◽

Vol 17 (6) ◽

pp. 459-465

Author(s):

Soghra Khabnadideh ◽

Zeinab Faghih ◽

Leila Zamani ◽

Kamiar Zomorodian ◽

Bi Bi Fatemeh Mirjalili ◽

...

Keyword(s):

Cell Lines ◽

Human Cancer ◽

Antimicrobial Activities ◽

Cytotoxic Agents ◽

Cytotoxic Activities ◽

Pyrazole Derivatives ◽

One Pot ◽

Human Cancer Cell Lines ◽

Cancerous Cell ◽

Anti Cancer

A simple and efficient method was developed for the synthesis of pyrazole derivatives via a one-pot reaction of 1,3-diketone and substituted hydrazines in the presence of nano-SnCl4/SiO2 as a mild catalyst. A series of some pyrazole derivatives (P1-P11) was synthesized and evaluated as antifungal and anti-cancer agents. Compounds P10 and P11 were demonstrated. The antimicrobial activities of the synthetic compounds showed that compounds P10 and P11 most excellently inhibited the growth of dermatophytes or Aspergillus species, respectively. Therefore, the cytotoxic activities of these compounds on two human cancer cell lines, A549 (lung cancer) and MCF-7 (breast cancer) were further assessed. Hence, results demonstrated that beside antifungal activity, P10 had also desirable cytotoxic effect on investigated cancerous cell lines, even higher than cisplatin.

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IN VITRO CYTOTOXICITY ASSAY, ANTIOXIDANT SCREENING AND HEPATOPROTECTIVE ACTIVITY OF SUCCESSIVE EXTRACTS OF ALYSICARPUS VAGINALIS VAR. NUMMULARIFOLIUS (DC.) MIQ. (FAMILY: FABACEAE) IN HEPG2 CELL LINES

International Journal of Biology Pharmacy and Allied Sciences ◽

10.31032/ijbpas/2021/10.1.5298 ◽

2021 ◽

Vol 10 (1) ◽

Keyword(s):

Hepg2 Cell ◽

Cell Lines ◽

Hepatoprotective Activity ◽

In Vitro Cytotoxicity ◽

Cytotoxicity Assay ◽

Hepg2 Cell Lines

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In vitro cellular models of human hepatic fatty acid metabolism: differences between Huh7 and HepG2 cell lines in human and fetal bovine culturing serum

Physiological Reports ◽

10.14814/phy2.13532 ◽

2017 ◽

Vol 5 (24) ◽

pp. e13532 ◽

Cited By ~ 17

Author(s):

Pippa J. Gunn ◽

Charlotte J. Green ◽

Camilla Pramfalk ◽

Leanne Hodson

Keyword(s):

Fatty Acid ◽

Hepg2 Cell ◽

Cell Lines ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Cellular Models ◽

Hepatic Fatty Acid ◽

Fetal Bovine ◽

Hepg2 Cell Lines

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Synthesis of 2-substituted Furo[3,2-b]pyridines Under Pd/C-Cu Catalysis Assisted by Ultrasound: Their Evaluation as Potential Cytotoxic Agents

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200311102304 ◽

2020 ◽

Vol 20 (8) ◽

pp. 932-940 ◽

Cited By ~ 1

Author(s):

Dandamudi Sri Laxmi ◽

Suryadevara V. Vardhini ◽

Venkata R. Guttikonda ◽

Mandava V.B. Rao ◽

Manojit Pal

Keyword(s):

Cell Lines ◽

Ultrasound Irradiation ◽

Cytotoxic Agents ◽

Direct Access ◽

Pyridine Derivative ◽

Anticancer Activities ◽

One Pot ◽

Anticancer Properties ◽

Mcf 7

Background: Compounds containing furo[3,2-b]pyridine framework have shown interesting pharmacological properties, including anticancer activities. Though these compounds are generally synthesized via the heteroannulation processes involving acetylenic derivatives, some of them are complex. Objective: The study aimed to explore a series of 2-substituted furo[3,2-b]pyridines for their cytotoxic properties against cancer cell lines in vitro. Methods: We developed a convenient synthesis of 2-substituted furo[3,2-b]pyridines via sequential (i) C-C coupling followed by (ii) C-O bond-forming reactions in a single pot. The reactions were performed under ultrasound irradiation in the presence of Pd/C as an inexpensive, stable and widely used catalyst. A range of 2- substituted furo[3,2-b]pyridines were synthesized via coupling of 3-chloro-2-hydroxy pyridine with terminal alkynes in the presence of 10% Pd/C-CuI-PPh3-Et3N in EtOH. The in vitro evaluation of all these compounds was carried out against MDA-MB-231 and MCF-7 cell lines and subsequently against SIRT1. Results: The furo[3,2-b]pyridine derivative 3b showed encouraging growth inhibition of both MDAMB-231 and MCF-7 cell lines and inhibition of SIRT1. The compound 3b also showed apoptosis-inducing potential when tested against MCF-7 cells. Conclusion: The Pd/C-Cu catalysis under ultrasound accomplished a one-pot and direct access to 2-substituted furo[3,2-b]pyridine derivatives, some of which showed anticancer properties.

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Synthesis, cytotoxicity and in silico study of some novel benzocoumarin-chalcone-bearing aryl ester derivatives and benzocoumarin-derived arylamide analogs

Zeitschrift für Naturforschung B ◽

10.1515/znb-2020-0204 ◽

2021 ◽

Vol 76 (3-4) ◽

pp. 201-210

Author(s):

Nabeel A. Abdul-Ridha ◽

Afraah D. Salmaan ◽

Rita Sabah ◽

Bahjat Saeed ◽

Najim A. Al-Masoudi

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Human Liver ◽

Hydrophobic Interactions ◽

Cytotoxic Agents ◽

Cytotoxic Activities ◽

Protein Receptor ◽

Normal Human Liver ◽

Normal Human

Abstract The development of new prostate cancer protein receptor cytochrome P450 17A1 inhibitors offers the possibility of generating structures of increased potency. To this end, the chalcone analogs 7 and 8 were prepared from treatment of methyl 3-oxo-3H-benzocoumarin-2-carboxylate (4) with aryl aldehydes. Treatment of 7 and 8 with three anti-inflammatory drugs, flurbiprofen, ketoprofen and ibuprofen, in the presence of POCl3/DMAP gave the ester analogs 9–12. Analogously, treatment of ethyl 3-oxo-3H-benzocoumarin-2-carboxylate (15), prepared previously from 2-hydroxy-1-naphthaldehyde (13) and dimethylmalonate (14), with various arylamines: 4-bromoaniline, 2-amino-6-methylpyridine, amino-antipyrine and 2-amino-5-nitrothiazole, in the presence of potassium tert-butoxide gave the benzocoumarine-3-arylamide analogs. The in vitro cytotoxic activities of 9–12 and 16–19 were evaluated against human prostate cancer cell lines (PC-3) and normal human liver epithelia (WRL-68) by MTT assay. Compounds 10 and 17 were the most active cytotoxic agents among the series against PC-3 cells with IC50 values of 71.35 and 78.25 μg mL–1 with SI values of 3.0 and 4.2, respectively (calculated from the cytotoxicity effects of 10 and 17 on the normal human liver epithelia [WRL-68]). Furthermore, compounds 11 and 12 were tested against breast cancer (HER2 cell lines), prostate cancer (DU-135 cell lines) and MCF-7 but were inactive. Molecular docking studies between the protein receptor CYPP450 17A1 and compounds 10 and 17 revealed that these compounds primarily form hydrophobic interactions with the receptor.

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Chemical Constituents of Tibetan Herbal Medicine Pulicaria insignis and Their in vitro Cytotoxic Activities

Records of Natural Products ◽

10.25135/rnp.193.20.06.1692 ◽

2020 ◽

Vol 15 (2) ◽

pp. 91-102

Author(s):

Xinzhu Wang ◽

Peilei Hou ◽

Yanbo Qu ◽

Rizhen Huang ◽

Yan Feng ◽

...

Keyword(s):

Herbal Medicine ◽

Cell Lines ◽

Hepg2 Cells ◽

Chemical Constituents ◽

2D Nmr ◽

Cytotoxic Activities ◽

Hela Cell Lines ◽

Ic50 Values ◽

Hepg2 Cell Lines

One new phenolic derivative, 1-(4',5'-dihydroxy-2'-methylphenyl)-pentane-1,4-dione (1), along with eighteen known compounds including eight sesquiterpenoids (2–9), one triterpenoid (10), one bisdpoxylignan (11), one coumarin (12), and seven flavonoids (13–19) were isolated from the dried inflorescence of Tibetan herbal medicine Pulicaria insignis. The structure of 1 was established by spectroscopic methods, including HRESIMS, IR, 1D, and 2D NMR. All isolates were assessed for the cytotoxic activities against MGC-803, T24, HepG2, and HeLa cell lines using the MTT assay. The results showed that compound 1 displayed moderate cytotoxicity against Hela and HepG2, and compounds 3, 4, 5, 6, and 13 exhibited potential cytotoxic activities against the four cell lines with IC50 values ranging from 3.05 to 14.37 μM. Notably, compound 5 exhibited significant anti-proliferative activities against HepG2 cell lines with the IC50 values of 3.05 ± 0.36 μM. Further bioactivity investigation showed that compound 5 could block HepG2 cells in the G1 phase of the cell cycle, thereby inhibiting the growth of HepG2 cells and inducing apoptosis in HepG2 cells.

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