Synthesis, Characterization and Cytotoxic Activity of New 2,9-BIS(2-Fluorobenzyl)-β-Carbolinium Bromide as a potential compound for anti-cancer agents

β-carbolines constitute a vast group of indole alkaloids and exhibit various biochemical effects and pharmacological properties. With the recent emergence of β-carboline in the field of cancer, this study investigated the synthesis, characterization, and potential anticancer activity of β-carboline derivative. An efficient method was described for the synthesis of new 2,9-bis(2-fluorobenzyl)-β-carbolinium bromide from L-tryptophan through the Pictet-Spengler reaction and oxidation of K2Cr2O7 by a sequential one-pot synthesis method then followed by N2, N9-benzylated using 2-fluorobezyl with good yield (92%). The structure of the compound was established by 1H-, 13C-NMR, and mass spectroscopy (ESI-MS) as well as single-crystal X-ray crystallographic analysis. The compound was tested for anticancer activity against Hela, HT-29, Hep-G2, and K562 cell lines by using MTT assay. 2,9-bis(2-fluorobenzyl)-β-carbolinium bromide exerted promising anticancer activities with IC50 values ranging between 0.97 to 6.00 μM as compared to doxorubicin which was employed as the positive control (0.77 μM). The results suggested that new, 2,9-bis(2-fluorobenzyl)-β-carbolinium bromide could potentially be developed as a novel anticancer agent.

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Novel Efficient Bioprocessing of Marine Chitins into Active Anticancer Prodigiosin

Marine Drugs ◽

10.3390/md18010015 ◽

2019 ◽

Vol 18 (1) ◽

pp. 15 ◽

Cited By ~ 9

Author(s):

Van Bon Nguyen ◽

Shan-Ping Chen ◽

Thi Hanh Nguyen ◽

Minh Trung Nguyen ◽

Thi Thanh Thao Tran ◽

...

Keyword(s):

Serratia Marcescens ◽

Bioactive Compound ◽

Potential Candidate ◽

Hep G2 ◽

Anticancer Activities ◽

Anti Cancer ◽

Initial Ph ◽

Ic50 Values ◽

First Time ◽

Mcf 7

Marine chitins (MC) have been utilized for the production of vast array of bioactive products, including chitooligomers, chitinase, chitosanase, antioxidants, anti-NO, and antidiabetic compounds. The aim of this study is the bioprocessing of MC into a potent anticancer compound, prodigiosin (PG), via microbial fermentation. This bioactive compound was produced by Serratia marcescens TKU011 with the highest yield of 4.62 mg/mL at the optimal conditions of liquid medium with initial pH of 5.65–6.15 containing 1% α-chitin, 0.6% casein, 0.05% K2HPO4, and 0.1% CaSO4. Fermentation was kept at 25 °C for 2 d. Notably, α-chitin was newly investigated as the major potential material for PG production via fermentation; the salt CaSO4 was also found to play the key role in the enhancement of PG yield of Serratia marcescens fermentation for the first time. PG was qualified and identified based on specific UV, MALDI-TOF MS analysis. In the biological activity tests, purified PG demonstrated potent anticancer activities against A549, Hep G2, MCF-7, and WiDr with the IC50 values of 0.06, 0.04, 0.04, and 0.2 µg/mL, respectively. Mytomycin C, a commercial anti-cancer compound was also tested for comparison purpose, showing weaker activity with the IC50 values of 0.11, 0.1, 0.14, and 0.15 µg/mL, respectively. As such, purified PG displayed higher 2.75-fold, 1.67-fold, and 3.25-fold efficacy than Mytomycin C against MCF-7, A549, and Hep G2, respectively. The results suggest that marine chitins are valuable sources for production of prodigiosin, a potential candidate for cancer drugs.

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First Synthesis for Bis-Spirothiazolidine Derivatives as a Novel Heterocyclic Framework and Their Biological Activity

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666190920114852 ◽

2020 ◽

Vol 20 (2) ◽

pp. 152-160

Author(s):

Eman M. Flefel ◽

Walaa I. El-Sofany ◽

Hanem M. Awad ◽

Mahmoud El-Shahat

Keyword(s):

Anticancer Activity ◽

Thioglycolic Acid ◽

Wide Spectrum ◽

Heterocyclic Ring ◽

Positive Control ◽

Liver Carcinoma ◽

Anticancer Activities ◽

One Pot ◽

Three Component Reaction ◽

Synthetic Scaffold

Background: Spirothiazolidines are versatile synthetic scaffold possessing wide spectrum of biological interests involving potential anticancer activity. Objectives: To report the first synthesis of Bis Spiro-thiazolidine as a novel heterocyclic ring system. Method: One-pot three-component reaction including condensation of p-phenyllene diamine; cyclohexanone and thioglycolic acid produced Spiro-thiazolidine 4, which underwent further condensation with cyclohexanone and thioglycolic acid with equimolar ratio to introduce Bis-Spiothiazolidine 5 as the first synthesis. Also, bis spiro-thiazolidine arylidene derivatives 6-13 were synthesized by the reaction of Bis-Spiothiazolidine 5 with different aromatic benzaldehydes. Results: Four compounds 13, 12, 9 and 11 have shown highly significant anticancer activity compared to Doxorubicin® (positive control) against Human liver carcinoma (HepG2) and Human Normal Retina pigmented epithelium (RPE-1) cell lines. Conclusion: The novel bis-spirothiazolidine deriviatives have been synthesized for the first time and showed excellent anticancer activities compare with the corresponding spirothiazolidine derivatives.

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Synthesis, DFT Calculations, Antiproliferative, Bactericidal Activity and Molecular Docking of Novel Mixed-Ligand Salen/8-Hydroxyquinoline Metal Complexes

Molecules ◽

10.3390/molecules26164725 ◽

2021 ◽

Vol 26 (16) ◽

pp. 4725

Author(s):

Badriah Saad Al-Farhan ◽

Maram T. Basha ◽

Laila H. Abdel Rahman ◽

Ahmed M. M. El-Saghier ◽

Doaa Abou El-Ezz ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Docking ◽

Metal Complexes ◽

Wide Spectrum ◽

Mixed Ligand ◽

Molecular Formula ◽

Hep G2 ◽

Anticancer Activities ◽

Azomethine Group ◽

Ic50 Values

Despite the common use of salens and hydroxyquinolines as therapeutic and bioactive agents, their metal complexes are still under development. Here, we report the synthesis of novel mixed-ligand metal complexes (MSQ) comprising salen (S), derived from (2,2′-{1,2-ethanediylbis[nitrilo(E) methylylidene]}diphenol, and 8-hydroxyquinoline (Q) with Co(II), Ni(II), Cd(II), Al(III), and La(III). The structures and properties of these MSQ metal complexes were investigated using molar conductivity, melting point, FTIR, 1H NMR, 13C NMR, UV–VIS, mass spectra, and thermal analysis. Quantum calculation, analytical, and experimental measurements seem to suggest the proposed structure of the compounds and its uncommon monobasic tridentate binding mode of salen via phenolic oxygen, azomethine group, and the NH group. The general molecular formula of MSQ metal complexes is [M(S)(Q)(H2O)] for M (II) = Co, Ni, and Cd or [M(S)(Q)(Cl)] and [M(S)(Q)(H2O)]Cl for M(III) = La and Al, respectively. Importantly, all prepared metal complexes were evaluated for their antimicrobial and anticancer activities. The metal complexes exhibited high cytotoxic potency against human breast cancer (MDA-MB231) and liver cancer (Hep-G2) cell lines. Among all MSQ metal complexes, CoSQ and LaSQ produced IC50 values (1.49 and 1.95 µM, respectively) that were comparable to that of cisplatin (1.55 µM) against Hep-G2 cells, whereas CdSQ and LaSQ had best potency against MDA-MB231 with IC50 values of 1.95 and 1.43 µM, respectively. Furthermore, the metal complexes exhibited significant antimicrobial activities against a wide spectrum of both Gram-positive and -negative bacterial and fungal strains. The antibacterial and antifungal efficacies for the MSQ metal complexes, the free S and Q ligands, and the standard drugs gentamycin and ketoconazole decreased in the order AlSQ > LaSQ > CdSQ > gentamycin > NiSQ > CoSQ > Q > S for antibacterial activity, and for antifungal activity followed the trend of LaSQ > AlSQ > CdSQ > ketoconazole > NiSQ > CoSQ > Q > S. Molecular docking studies were performed to investigate the binding of the synthesized compounds with breast cancer oxidoreductase (PDB ID: 3HB5). According to the data obtained, the most probable coordination geometry is octahedral for all the metal complexes. The molecular and electronic structures of the metal complexes were optimized theoretically, and their quantum chemical parameters were calculated. PXRD results for the Cd(II) and La(III) metal complexes indicated that they were crystalline in nature.

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A nitroalkane-based approach to one-pot three-component synthesis of isocryptolepine and its analogs with potent anti-cancer activities

RSC Advances ◽

10.1039/c8ra08155g ◽

2018 ◽

Vol 8 (64) ◽

pp. 36980-36986 ◽

Cited By ~ 5

Author(s):

Nicolai A. Aksenov ◽

Alexander V. Aksenov ◽

Alexander Kornienko ◽

Annelise De Carvalho ◽

Véronique Mathieu ◽

...

Keyword(s):

Anticancer Activities ◽

One Pot ◽

Anti Cancer

An improved one-pot three-component synthesis involving electrophilically activated nitroalkanes allowed for efficient preparation of indoloquinolines with potent anticancer activities.

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A New Potent Anti-cancer Corosolic Ester Identified from the Super Miracle Plant Hippophae rhamnoides (Sea buckthorn)

Biochemistry and Modern Applications ◽

10.33805/2638-7735.119 ◽

2019 ◽

pp. 24-29

Author(s):

Irfan Ali ◽

Noor-ul-Ain Zahra ◽

Reazuddin R ◽

Huma Sharif ◽

Mudassar M ◽

...

Keyword(s):

Anticancer Activity ◽

Cancer Cell ◽

Weak Interactions ◽

Cancer Cell Line ◽

Lung Cancer Cell Line ◽

Sea Buckthorn ◽

Hippophae Rhamnoides ◽

Hippophaë Rhamnoides ◽

Anti Cancer ◽

Ic50 Values

Hippophae rhamnoides L, commonly called Sea buckthorn, is native to Asia and Europe and and known for its nutritional and medicinal values. The aim of the present study was to investigate the anti-cancer constituents of H. rhamnoides. Among the three isolated compounds namely: 1-(2-hydroxynaphthalen-1-yl) ethan-1-one (1), Oleanolic acid (2), and Hippocorosolate (3), compound 3 was a new corosolic ester derivative. The isolated compounds (2 and 3) displayed anticancer activity against lung (NCI-H460) and breast (MCF-7) cancer cell lines with IC50 values of ~3 µM and ~6 µM, respectively. However, compound 1 was active only against breast cancer cells with IC50 value of ~43 µM. These compounds displayed only weak interactions with minor groove of DNA in DNA-ligand conformational studies and therefore, structural DNA damage was not noted in electrophoretic mobility experiments. It was concluded that new compound 2 possessed more potent anticancer activity than that of known compound 3 against lung cancer cell line.

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Telomere DNA Binding, Cleavage and Anticancer Activity of [Cu(phendione)(Hpyramol)Cl]

Current Chemical Biology ◽

10.2174/2212796813666190214112129 ◽

2019 ◽

Vol 13 (2) ◽

pp. 171-182

Author(s):

Palanisamy Uma Maheswari ◽

Renuga Duraisamy ◽

Murugesan Kanagavel ◽

Kalimuthusamy Natarajaseenivasan ◽

Kadhar Mohamed Meera Sheriffa Begum ◽

...

Keyword(s):

Anticancer Activity ◽

Cancer Cells ◽

Dna Cleavage ◽

Phenoxyl Radical ◽

Anticancer Activities ◽

Redox Active ◽

G Quadruplex ◽

Ic50 Values ◽

Controlled Potential ◽

Human Telomere

Background:The ligand Hpyramol is a redox active, which on coordination with Cu(II) cleaves DNA without any added reductant. Another ligand phendione is known for its wide application towards anticancer activities. We combined the ligands with CuCl2 to have an intercalation moiety and a redox active ligand in participation towards telomere DNA cleavage and anticancer activity.Objective:In this study, our aim is to interact it with Human telomere DNA and to see their effects on cancer cells.Methods:The complex [Cu(L)(L’)Cl] has interacted with the human telomere DNA sequence (TTAGGG), HTelo20. The HTelo20 was stabilized under both parallel and antiparallel G-quadruplex conformations and the complex [Cu(L)(L’)Cl] has interacted followed by circular dichroism spectroscopy and gel electrophoresis.Results:The parallel G-quadruplex and randomly coiled conformations of HTelo20 were easily cleaved than the anti-parallel G-quadruplex conformation. The nature of DNA cleavage was found to be oxidative rather hydrolytic. The formation of phenoxyl radical species under electrochemical and controlled potential electrolysis conditions by the complex [Cu(L)(L’)Cl] proves the possibility of oxidative nature of DNA cleavage. The comet assay also proves the DNA cleavage induced by the complex [Cu(L)(L’)Cl] inside the nucleus of HeLa cancer cells.Conclusion:The complex [Cu(L)(L’)Cl] was tested for anticancer activity, induced by ROS and DNA cleavage. The IC50 values resulted in nanomolar concentrations with selected cancer cell lines. Relatively the Cu complex shows less toxicity with the normal cell line L132.

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Thiazolidinedione or Rhodanine: A Study on Synthesis and Anticancer Activity Comparison of Novel Thiazole Derivatives

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j38p9r ◽

2017 ◽

Vol 20 (1) ◽

pp. 415 ◽

Cited By ~ 6

Author(s):

Cigdem Ozen ◽

Meltem Ceylan Unlusoy ◽

Nazanin Aliary ◽

Mehmet Ozturk ◽

Oya Bozdag Dundar

Keyword(s):

Hepatocellular Carcinoma ◽

Anticancer Activity ◽

Cell Line ◽

Cell Lines ◽

Condensation Reaction ◽

Huh7 Cell ◽

Anticancer Activities ◽

Thiazole Derivatives ◽

Ic50 Values ◽

Huh7 Cell Line

Purpose: A new series of thiazolyl-2,4-thiazolidinedione / rhodanine compounds T1-T23 was synthesized and tested for their anticancer activities. Hepatocellular carcinoma cell lines were chosen due to their strong drug resistance to test the new compounds. Methods: All compounds were synthesized via Knoevenagel Condensation reaction and thiazolidinedione ester compounds (T3,T9,T15,T20) were hydrolyzed for obtaining the acidic compounds (T6,T12,T17,T23). All compounds were firstly screened for their anticancer activity against two hepatocellular carcinoma (HCC) cell lines, Huh7 and Plc/Prf/5 (Plc) cell lines by sulforhodamine B assay. Further IC50 values were calculated for three candidates (T4, T15, T21) in five different HCC (Huh7, Plc, Snu449, HepG2, Hep3B) and one breast cancer (Mcf7) cell line. Results: Compounds T4, T15, T21 had very strong anticancer effects even though their 10 µM concentration in Huh7 cell line. According to IC50 values, T21 was the most effective compound with IC50 values in a range from 2 to 16 µM in 6 cancer cell lines. In terms of cytotoxicity T21 mostly affected Huh7 and interestingly it was less effective against Plc. Conclusions: Considering these results it can be suggested that compounds T4, T15 and T21 may lead to the development of more potent anticancer drugs in the future. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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SYNTHESIS, CHARACTERIZATION AND CYTOTOXIC ACTIVITY OF Pt(II)COMPLEX OF CAMPHOR 4-METHYL THIOSEMICARBAZONE

Vietnam Journal of Science and Technology ◽

10.15625/2525-2518/56/2a/12632 ◽

2018 ◽

Vol 56 (2A) ◽

pp. 75-80

Author(s):

Phan Thi Hong Tuyet

Keyword(s):

Cytotoxic Activity ◽

Cancer Cells ◽

1H Nmr ◽

Biomedical Application ◽

Molecular Formula ◽

Hep G2 ◽

Anti Cancer ◽

Ic50 Values ◽

Cancer Activity

The new complex of Pt(II) with camphor 4-methyl thiosemicarbazone was synthesized and characterized by means of MS, 1H-NMR and IR spectroscopes. Results show that, the molecular formula of new Pt(II) complex is [Pt(C12H20N3S))2]. The Pt(II) complex is of four coordinate. The result of in vitro anti-cancer activity of the complex has shown that the complex of Pt(II) with camphor 4-methyl thiosemicarbazone exhibit inhibitor on Hep-G2 and RD cancer cells with IC50 values of 7.74 and 7.61 µg.mL-1. These results indicated a potential of new Pt(II)complex in biomedical application.

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Design, Synthesis and Anticancer Evaluation of Acetamides Comprising 1,2,3-triazole, 1,3,4-thiadiazole and Isothiazolo[4,3-b]pyridine Rings

Letters in Organic Chemistry ◽

10.2174/1570178617666200225102939 ◽

2020 ◽

Vol 17 (11) ◽

pp. 864-871 ◽

Cited By ~ 2

Author(s):

Shaik Shahinshavali ◽

Nuthalapati Poojith ◽

Venkat Rao Guttikonda ◽

Reddymasu Sreenivasulu ◽

Mandava Venkata Basaveswara Rao

Keyword(s):

Breast Cancer ◽

Human Cancer ◽

Positive Control ◽

Pyridine Derivatives ◽

Anticancer Activities ◽

Design Synthesis ◽

Human Cancer Cell Lines ◽

Ic50 Values ◽

A549 Lung ◽

Mcf 7

We have synthesized a library of new 1,2,3-triazole incorporated 1,3,4-thiadiazoleisothiazolo[ 4,3-b]pyridine derivatives 12a-j and have screened these products for their anticancer activities against four human cancer cell lines such as MCF-7 (breast cancer), A549 (lung cancer), DU-145 (prostate cancer), and MDA MB-231 (breast cancer) using MTT assay with etoposide as a positive control. Among them, compound 12e has shown excellent activities against MCF-7, A549, DU-145, and MDA-MB-231 with IC50 values of 0.53±0.055 μM, 0.18±0.077 μM, 0.10±0.082 μM, and 0.92±0.041 μM, respectively.

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Anti-Liver and Anti-Breast Cancer Activities of Novel 2-Thioxo-4-Imidazolidinone Derivatives

10.21203/rs.3.rs-488343/v1 ◽

2021 ◽

Author(s):

Layla Adnan AbdulJabar ◽

Ali AlShawi ◽

Dakhil Zughayir Mutlaq

Keyword(s):

Breast Cancer ◽

Anticancer Activity ◽

Cancer Cells ◽

Hepg2 Cells ◽

Positive Control ◽

S Phase ◽

Phase Compound ◽

Ic50 Values ◽

Late Apoptosis ◽

Mcf 7

Abstract MTT assay and flowcytometry analysis were used to examine the anti-liver (HepG2) and anti-breast cancer (MCF-7) activities of twelve compounds derived from 2-thioxo-4-imidazolidine. The compounds 5a-h and 7f demonstrated significant anticancer activity against breast cancer cells, while the compounds 5a, ab, and 5d-h demonstrated significant anticancer activity against liver cancer cells, with varying IC50 values as compared to Cisplatin as the positive control. Among these compounds, we chose 5a, 5d, and 5h to detect cell cycle phases and late apoptosis. Compound 5a arrested MCF-7 cells in the S phase, while compound 5d arrested cells in the G1 phase. Compound 5a arrested S phase HepG2 cells, compound 5d arrested S phase cells, and compound 5h arrested G2 phase HepG2 cells. Compound 5a had a higher ratio of late apoptosis than compounds 5d and 5h on both cancer cells. Finally, the development of these compounds as new anti-breast and anti-liver agents warrants further research to understand the mechanism of action, especially against breast cancer.

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