Ultrasound Assisted Synthesis of 2-Substituted Benzofurans via One-Pot and Sequential Method: Their In Vitro Evaluation

2020 ◽  
Vol 20 (5) ◽  
pp. 580-588
Author(s):  
Bodapati V.D. Rao ◽  
Suryadevara V. Vardhini ◽  
Deepti Kolli ◽  
Mandava V.B. Rao ◽  
Manojit Pal
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Bond Cleavage ◽  
Cancer Cell Lines ◽  
Significant Inhibition ◽  
Direct Access ◽  
Sequential Method ◽  
One Pot ◽  
Mcf 7

Background: The 2-substituted benzofuran framework has attracted enormous attention due to its presence in a range of bioactive compounds and natural products. While various methods for the synthesis of 2- substituted benzofuran derivatives are known, several of them suffer from certain drawbacks. Objective: The main objective of this work was to explore a series of 2-(het)aryl substituted benzofurans derivatives for their cytotoxic properties against cancer cell lines in vitro. Methods: In our efforts, we have developed a one-pot synthesis of this class of compounds via sequential C-C coupling followed by C-Si bond cleavage and subsequent tandem C-C/C-O bond-forming reaction under ultrasound irradiation. The methodology involved coupling of (trimethylsilyl)acetylene with iodoarenes in the presence of 10% Pd/C-CuI-PPh3-Et3N in MeOH followed by treating the reaction mixture with K2CO3 in aqueous MeOH and finally coupling with 2-iodophenol. A variety of 2-substituted benzofurans were synthesized using this methodology in good yield. All the synthesized compounds were tested in vitro against two cancer cell lines, e.g. MDAMB-231 and MCF-7 cell lines subsequently against SIRT1. Results: The benzofuran derivative 3m showed encouraging growth inhibition of both MDAMB-231 and MCF- 7 cell lines and significant inhibition of SIRT1. The compound 3m also showed a concentration-dependent increase in the acetylation of p53. Conclusion: Our efforts not only accomplished a one-pot and direct access to 2-(het)aryl substituted benzofurans but also revealed that the benzofuran framework presented here could be a potential template for the identification of potent inhibitors of SIRT1.

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

2020 ◽  
Vol 10 (6) ◽  
pp. 2170 ◽  
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.

In Vitro Antitumor Evaluation of Some Hybrid Molecules Containing Coumarin and Quinolinone Moieties

2020 ◽  
Vol 19 (16) ◽  
pp. 2010-2018
Author(s):  
Youstina W. Rizzk ◽  
Ibrahim M. El-Deen ◽  
Faten Z. Mohammed ◽  
Moustafa S. Abdelhamid ◽  
Amgad I.M. Khedr
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Cancer Cell Lines ◽  
Bax Protein ◽  
Hybrid Molecules ◽  
Mcf 7

Background: Hybrid molecules furnished by merging two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery. Currently, coumarin hybrids have attracted the keen attention of researchers to discover their therapeutic capability against cancer. Objective: The present study aimed to evaluate the in vitro antitumor activity of a new series of hybrid molecules containing coumarin and quinolinone moieties 4 and 5 against four cancer cell lines. Materials and Methods: A new series of hybrid molecules containing coumarin and quinolinone moieties, 4a-c and 5a-c, were synthesized and screened for their cytotoxicity against prostate PC-3, breast MCF-7, colon HCT- 116 and liver HepG2 cancer cell lines as well as normal breast Hs-371 T. Results: All the synthesized compounds were assessed for their in vitro antiproliferative activity against four cancer cell lines and several compounds were found to be active. Further in vitro cell cycle study of compounds 4a and 5a revealed MCF-7 cells arrest at G2 /M phase of the cell cycle profile and induction apoptosis at pre-G1 phase. The apoptosis-inducing activity was evidenced by up-regulation of Bax protein together with the downregulation of the expression of Bcl-2 protein. The mechanism of cytotoxic activity of compounds 4a and 5a correlated to its topoisomerase II inhibitory activity. Conclusion: Hybrid molecules containing coumarin and quinolinone moieties represents a scaffold for further optimization to obtain promising anticancer agents.

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

Molecules ◽  
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.

scholarly journals In vitro investigation of cytotoxic and antioxidative activities of Ardisia crispa against breast cancer cell lines, MCF-7 and MDA-MB-231

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Muhammad Luqman Nordin ◽  
Arifah Abdul Kadir ◽  
Zainul Amiruddin Zakaria ◽  
Rasedee Abdullah ◽  
Muhammad Nazrul Hakim Abdullah
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
In Vitro Investigation ◽  
Ardisia Crispa ◽  
Mcf 7

scholarly journals Synthesis and Biological Activity of 2-Arylidene-N-(quinolin-6-yl)hydrazine-1-carboxamides

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shengxian Zhao ◽  
Yin Cao ◽  
Zhenzhen Cui ◽  
Jiayun Zhang ◽  
Zhixiang Pan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Colony Formation Assay ◽  
M Phase ◽  
Antiproliferative Activities ◽  
Mcf 7

A series of 2-arylidene-N-(quinolin-6-yl)hydrazine-1-carboxamides 5a–5o were synthesized and characterized. The synthesized compounds (5a–5o) were screened in vitro against three breast cancer cell lines: SKBR3, MDA-MB-231, and MCF-7 cancer cell lines by the MTT assay. According to MTT results, compounds 5k and 5l showed better antiproliferative activities over MCF-7 cell lines with IC50 values of 8.50 and 12.51 μM. Colony formation assay indicated 5k/5l treatment obviously inhibited the growth of MCF-7 cells and 5k/5l-induced cell cycle was arrested in the G2-M phase. Moreover, 5k/5l significantly increased the level of cleaved PARP and induced the apoptosis in MCF-7 cells. In addition, compared to Hela cells, MCF-7 cells were more sensitive to 5k/5l treatment.

Anticancer and antioxidant studies of the methanol extract and fractions of Conyza sumatrensis (retz.) E. H. Walker (asteraceae

2020 ◽  
Vol 23 ◽  
pp. 77-82
Author(s):  
E.O. Ikpefan ◽  
B.A. Ayinde ◽  
B.A. Mudassar ◽  
Ahsana Dar Farooq
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Antioxidant Activities ◽  
Cancer Cell Lines ◽  
Total Phenolic ◽  
Chloroform Fraction ◽  
Aqueous Fraction ◽  
Growth Inhibitory ◽  
Mcf 7

The in vitro antiproliferative and antioxidant studies of the leaf extract and fractions of Conyza sumatrensis was investigated by applying the Sulforhodamine-B and 2, 2-diphenyl-1-picrylhydrazyl assays (DPPH-RSA) respectively. While the antiproliferative activity was carried out at 1-250 and 1-100 μg/ mL for the extract and fractions against breast (MCF-7) and lung (NCI-H460) cancer cell lines, the antioxidant study was conducted using DPPH at 31.25 -500 μg/ mL with the total phenolic and flavonoid contents calculated as well with reference to quercetin and gallic acid respectively. The extract and fractions were observed to elicit cytotoxic and growth inhibitory effects against breast (MCF-7) and lung cancer cell lines (NCI-H460) respectively. At 250 μg/mL, the extract of C. sumatrensis gave cytotoxicity of –1.76 ± 0.20 % against MCF-7 cell lines and inhibited growth of NCI-H460 at +94.40 ± 1.0 % respectively. While the chloroform fraction at 100 μg/mL gave -5.38 ± 0.33 % and 91 ± 1.61 % against MCF-7 and NCI-H460 cell lines, the aqueous fraction was observed to be inactive. For the DPPH-RSA activity, the chloroform fraction demonstrated an IC50 value of 125.5 μg/ mL compare to quercetin at 62.5 μg/ mL. The bioactivities were more pronounced in the chloroform fraction. This work has shown that C.  sumatrensis has antiproliferative and antioxidant activities which could be tied to the secondary metabolites present in the plant.

scholarly journals Synthesis, Characterization, and In Vitro Cancer Cell Growth Inhibition Evaluation of Novel Phosphatidylcholines with Anisic and Veratric Acids

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2022 ◽  
Author(s):  
Marta Czarnecka ◽  
Marta Świtalska ◽  
Joanna Wietrzyk ◽  
Gabriela Maciejewska ◽  
Anna Gliszczyńska
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Organism ◽  
Cancer Cell Growth ◽  
Anticancer Properties ◽  
Health Promoting ◽  
Phenolcarboxylic Acids ◽  
Mcf 7

Phenolic acids and its methoxy derivatives are known to induce caspase-mediated apoptosis activity and exhibit cytotoxic effect towards various cancer cell lines. However, their low stability and poor bioavailability in the human organism extensively restrict the utility of this group of compounds as anticancer and health-promoting agents. In this report, a series of eight novel phosphatidylcholines (3a-b, 5a-b, 7a-b, 8a-b) containing anisic or veratric acids (1a-b) at sn-1 and/or sn-2 positions were synthesized. The phenoylated phospholipids were obtained in good yields 28–66%. The structures of novel compounds were determined by their spectroscopic data. All synthesized compounds were evaluated for their antiproliferative activity towards six cancer cell lines and normal cell line Balb/3T3. Lipophilization of phenolcarboxylic acids significantly increased their anticancer properties. The asymmetrically substituted phenoylated phosphatidylcholines exhibited higher antiproliferative effect than free acids. Lysophosphatidylcholine (7b) effectively inhibited the proliferation of human leukaemia (MV4-11), breast (MCF-7), and colon (LoVo) cancer cell lines at concentrations of 9.5–20.7 µm and was from 19 to 38-fold more active than corresponding free veratric acid. The conjugation of anisic/veratric acids with the phosphatidylcholine have proved the anticancer potential of these phenolcarboxylic acids and showed that this type of lipophilization is an effective method for the production of active biomolecules.

scholarly journals Novel Tl(III) complexes containing pyridine-2,6-dicarboxylate derivatives with selective anticancer activity through inducing mitochondria-mediated apoptosis in A375 cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara Abdolmaleki ◽  
Mohammad Ghadermazi ◽  
Alireza Aliabadi
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Metal Salt ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Cancer Cell Lines ◽  
Triangular Prism ◽  
One Pot ◽  
A375 Cells

AbstractThree novel Tl(III) complexes (C1), (C2) and (C3) were synthesized using the one-pot reactions of pyridine dicarboxylic acid derivatives, 2-aminobenzimidazole and/or 4-aminopyridine, and also thallium(III) nitrate trihydrate metal salt. The structure of all three complexes was determined by the single-crystal X-ray diffraction. C1 and C2 were realized to be isostructural with disordered square anti-prismatic geometry and for C3 arrangement of the distorted tricapped triangular prism was proposed. Cyclic voltammetry measurements on the complexes exhibited that formal potential values are more positive for C1 (E0ˊ 0.109 V) and C3 (E0ˊ 0.244 V) compared to C2 (E0ˊ –0.051 V), versus Ag/AgCl under argon. Moreover, cytotoxicity of the compounds was evaluated in vitro against two cancer cell lines including a human melanoma (A375), a human colon adenocarcinoma (HT29), and also one normal cell human foreskin fibroblast (HFF). The selective and potent cytotoxicity effect was exhibited by C1 and C3 on cancer cell lines. The apoptosis through a caspase-dependent mitochondrion pathway was confirmed by ROS production, MMP reduction, p53 activation, Bax up-regulation, and Bcl-2 down-regulation, cytochrome c release, procaspase-9, and 3 expression, for A375 cells treated to C1 and C3. According to similar cellular uptake of the complexes in A375 cell line, the generation of ROS was considered as an effective agent to justify the inhibition effect C1 and C3 on mentioned cells. Furthermore, arresting the cell cycle in the G2-M phase and inducing apoptosis were indicated by these two complexes.

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