Evaluation of Cytotoxicity and α-Glucosidase Inhibitory Activity of Amide and Polyamino-Derivatives of Lupane Triterpenoids

A series of two new and twenty earlier synthesized branched extra-amino-triterpenoids obtained by the direct coupling of betulinic/betulonic acids with polymethylenpolyamines, or by the cyanoethylation of lupane type alcohols, oximes, amines, and amides with the following reduction were evaluated for cytotoxicity toward the NCI-60 cancer cell line panel, α-glucosidase inhibitory, and antimicrobial activities. Lupane carboxamides, conjugates with diaminopropane, triethylenetetramine, and branched C3-cyanoethylated polyamine methyl betulonate showed high cytotoxic activity against most of the tested cancer cell lines with GI50 that ranged from 1.09 to 54.40 µM. Betulonic acid C28-conjugate with triethylenetetramine and C3,C28-bis-aminopropoxy-betulin were found to be potent micromolar inhibitors of yeast α-glucosidase and to simultaneously inhibit the endosomal reticulum α-glucosidase, rendering them as potentially capable to suppress tumor invasiveness and neovascularization, in addition to the direct cytotoxicity. Plausible mechanisms of cytotoxic action and underlying disrupted molecular pathways were elucidated with CellMinner pattern analysis and Gene Ontology enrichment analysis, according to which the lead compounds exert multi-target antiproliferative activity associated with oxidative stress induction and chromatin structure alteration. The betulonic acid diethylentriamine conjugate showed partial activity against methicillin-resistant S. aureus and the fungi C. neoformans. These results show that triterpenic polyamines, being analogs of steroidal squalamine and trodusquemine, are important substances for the search of new drugs with anticancer, antidiabetic, and antimicrobial activities.

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Synthesis, Docking Study, Cytotoxicity, Antioxidant, and Anti-microbial Activities of Novel 2,4-Disubstituted Thiazoles Based on Phenothiazine

Current Organic Synthesis ◽

10.2174/1570179417666191220100614 ◽

2020 ◽

Vol 17 (2) ◽

pp. 151-159

Author(s):

Tran Nguyen Minh An ◽

Pham Thai Phuong ◽

Nguyen Minh Quang ◽

Nguyen Van Son ◽

Nguyen Van Cuong ◽

...

Keyword(s):

Cell Line ◽

Cancer Cell ◽

Cancer Cell Line ◽

Antimicrobial Activities ◽

Significant Activity ◽

Thiazole Derivatives ◽

Ligand Interaction ◽

Ic50 Value ◽

Mcf 7

: A series of novel 1,3-thiazole derivatives (5a-i) with a modified phenothiazine moiety were synthesized and tested against cancer cell line MCF-7 for their cytotoxicity. Most of them (5a-i) were less cytotoxic or had no activity against MCF-7 cancer cell line. Material and Methods: The IC50 value of compound (4) was 33.84 μM. The compounds (5a-i) were also evaluated for antimicrobial activities, but no significant activity was observed. The antioxidant activity was conducted for target compounds (5a-i). The IC50 value of compound (5b) was 0.151mM. Results: The total amount of energy, ACE (atomic contact energy), energy of receptor (PDB: 5G5J), and ligand interaction of structure (4) were found to be 22.448 Kcal.mol-1 , -247.68, and -91.91 Kcal.mol-1, respectively. The structure (4) is well binded with the receptor because the values of binding energy, steric energy, and the number of hydrogen bondings are -91.91, 22.448 kcal.mol-1, and 2, respectively. It shows that structure (4) has good cytotoxicity with MCF-7 in vitro. Conclusion: The increasing of docking ability of structures (5a-i) with the receptor is presented in increasing order as (5f)>(5e)>(5g)>(5a)>(5b)>(5d)>(5c)>(5i)>(5h). The structure bearing substitution as thiosemicarbazone (4), nitrogen heterocyclic (5f), halogen (5e), and azide (5g) showed good cytotoxicity activity in vitro.

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A Profile of the Biological Activity of Functionalized Benzimidazolium Ionic Liquids

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2020.13.5.9 ◽

2020 ◽

Vol 13 (5) ◽

pp. 5120-5130

Author(s):

Paul Metilda ◽

Starling P Jebha

Keyword(s):

Ionic Liquids ◽

Cell Line ◽

Cancer Cell ◽

Kojic Acid ◽

Bacterial Species ◽

Cancer Cell Line ◽

Biologically Active ◽

New Drugs ◽

Human Leukemia ◽

Pharmaceutical Industries

Now-a-days, the pharmaceutical industries were facing many challenges that impose the need to develop innovative and effective therapies. Hence, the investigation of effective therapies for cancer is an actual goal of every pharmaceutical industries. Recently, Ionic Liquids (ILs) have been considered as potential target in scientific community because of their unique performance in various fields. Moreover, numerous combinations made between the cation and the anion, which can be tuned the physicochemical and biological properties of ILs. Especially, these ionic liquids play a vital role for designing new drugs and producing potent bioactivity. Herein we synthesized a series of benzimidazolium based ionic liquids with different functional groups and their structure was confirmed by FT-IR, 1H NMR, 13C NMR as well as High resolution Mass spectroscopy technique antimicrobial activity of ILs were screened by five bacterial and fungal strains which was measured in terms of zone of inhibition. All the compounds were found to be effective against all bacterial species and fungi Candida albicans. Moreover, the total antioxidant capacity of ILs has been evaluated by Phosphomolybdenum method. The report indicates that kojic acid functionalized ILs exhibited significant antioxidant activity. In addition, antitumor activity of these compounds has been analyzed using human ovarian cancer cell line SK-OV-3, human prostate cancer cell line DU-145 and human leukemia cancer cell line K-562. The data obtained from antitumour studies showed that an excellent activity of ester functionalized ionic liquid confirms that can be used as an anticancer agent. However, ester functionalized and kojic acid functionalized ILs possess biologically active against the tested strains.

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Two new glycosidal metabolites of endophytic fungus Penicillium sp. (NO.4) from Tapiscia sinensis

Zeitschrift für Naturforschung B ◽

10.1515/znb-2015-0184 ◽

2016 ◽

Vol 71 (4) ◽

pp. 283-286 ◽

Cited By ~ 5

Author(s):

Qiao Wan ◽

Ziwei Feng ◽

Xueshuang Li ◽

Mengmeng Lv ◽

Zhiyong Guo ◽

...

Keyword(s):

Methyl Ester ◽

Cell Lines ◽

Cancer Cell ◽

Endophytic Fungus ◽

Cancer Cell Line ◽

2D Nmr ◽

Cancer Cell Lines ◽

Antimicrobial Activities ◽

Cytotoxic Activities ◽

A549 Cancer Cell Line

AbstractTwo new glycosides, 8-O-β-d-glucopyranosyl-6-methyl-1-carboxylate methyl ester xanthone (1) and 4′-O-β-d-galactopyranosyl djalonensone (2), together with four known compounds, 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate methyl ester (3), cassionllin (4), djalonensone (5) and alternariol (6), were isolated from the endophytic fungus Penicillium sp. (NO.4) of Tapiscia sinensis Oliv. The structures of compounds 1–6 were elucidated by the analysis of 1D and 2D NMR and HRMS. The cytotoxic activities of these compounds were evaluated against four cancer cell lines, as well as antimicrobial activities against two plant-pathogenic microbes. Compounds 1–6 showed moderate cytotoxicity against the A549 cancer cell line with IC50 values ranging from 6.8 to 35.8 μg mL−1 and were found to be inactive against three other cancer cell lines MCF-7, Caski and Hep G-2.

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Dispirooxindoles Based on 2-Selenoxo-Imidazolidin-4-Ones: Synthesis, Cytotoxicity and ROS Generation Ability

International Journal of Molecular Sciences ◽

10.3390/ijms22052613 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2613

Author(s):

Vladimir K. Novotortsev ◽

Maxim E. Kukushkin ◽

Viktor A. Tafeenko ◽

Dmitry A. Skvortsov ◽

Marina A. Kalinina ◽

...

Keyword(s):

Cell Line ◽

Cancer Cell ◽

Cancer Cell Line ◽

In Vitro Cytotoxicity ◽

Selectivity Index ◽

Azomethine Ylides ◽

Ros Generation ◽

Cytotoxic Action ◽

Diphenyl Tetrazolium Bromide

A regio- and diastereoselective synthesis of two types of dispiro derivatives of 2-selenoxoimidazolidin-4-ones, differing in the position of the nitrogen atom in the central pyrrolidine ring of the spiro-fused system—namely, 2-selenoxodispiro[imidazolidine-4,3′-pyrrolidine-2′,3″-indoline]-2″,5-diones (5a-h) and 2-senenoxodispiro[imidazolidine-4,3′-pyrrolidine-4′,3″-indoline]-2″,5-diones (6a-m)—were developed based on a 1,3-dipolar cycloaddition of azomethine ylides generated from isatin and sarcosine or formaldehyde and sarcosine to 5-arylidene or 5-indolidene-2-selenoxo-tetrahydro-4H-imidazole-4-ones. Selenium-containing dispiro indolinones generally exhibit cytotoxic activity near to the activity of the corresponding oxygen and sulfur-containing derivatives. Compounds 5b, 5c, and 5e demonstrated considerable in vitro cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) test (concentration of compounds that caused 50% death of cells (CC50) 7.6–8.7 μM) against the A549 cancer cell line with the VA13/A549 selectivity index 5.2–6.9 and compound 6e—against the MCF7 cancer cell line (CC50 20.6 μM, HEK293T/A549 selectivity index 1.6); some compounds (5 and 6) increased the level of intracellular reactive oxygen species (ROS) in the experiment on A549 and PC3 cells using platinized carbon nanoelectrode. The tests for p53 activation for compounds 5 and 6 on the transcriptional reporter suggest that the investigated compounds can only have an indirect p53-dependent mechanism of action. For the compounds 5b, 6b, and 6l, the ROS generation may be one of the significant mechanisms of their cytotoxic action.

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Synthesis, Characterization, Antimicrobial Activity and Anticancer of Some New Pyrazolo[1,5-a]pyrimidines and Pyrazolo[5,1-c]1,2,4-triazines

Medicinal Chemistry ◽

10.2174/1573406415666190620144404 ◽

2020 ◽

Vol 16 (6) ◽

pp. 750-760

Author(s):

Mona A. Hosny ◽

Yasser H. Zaki ◽

Wafaa A. Mokbel ◽

Abdou O. Abdelhamid

Keyword(s):

Cell Line ◽

Cancer Cell ◽

Cancer Cell Line ◽

Antimicrobial Activities ◽

Viability Assay ◽

Active Methylene Compounds ◽

Hct 116 ◽

Active Methylene ◽

Mcf 7

Background: Pyrazole and its derivatives are known to exhibit significant biological and pharmacological activities such as anticancer, anti-inflammatory, antioxidant, antibacterial, analgesic, antiviral, antimicrobial, antifungal, anti-glycemic, antiamoebic, and antidepressive. Considering the immense biological properties, pyrazole is one of the most widely studied nitrogen- containing heterocyclic nuclei. Fused pyrazole derivatives are composed of the pyrazole nucleus attached to other heterocyclic moieties. Objective: The objective of this article is the synthesis of some new pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c]1,2,4-triazine derivatives with potential anticancer and antimicrobial activities. Methods: The in vitro growth inhibitory rates (%) and inhibitory growth activity (as measured by IC50) of the newly synthesized compounds were determined against the MCF-7 human breast carcinoma cell line in comparison with the well-known anticancer drug doxorubicin as the standard, using the MTT viability assay. The data generated were used to plot a dose-response curve from which the concentration (μM) of tested compounds required to kill 50% of the cell population (IC50) was determined. Cytotoxic activity was expressed as the mean IC50 of three independent experiments. The difference between inhibitory activities of all compounds with different concentrations was statistically significant p < 0.001. All compounds were structurally characterized by different spectroscopic techniques EI-MS, 1H-NMR, and 13C-NMR, and evaluated for their anticancer and antimicrobial activities (antibacterial and antifungal). Results: Several pyrazolo[1,5-a]pyrimidine derivatives were synthesized from the reaction of 2-(4- (5-amino-1H-pyrazol-3-yl)phenyl)-1H-indene-1,3(2H)-dione with the appropriate active methylene compounds in boiling ethanol. Also, pyrazolo[5,1-c]triazines were obtained through the reaction of 2-(4-(5-(chlorodiazenyl)-1H-pyrazol-3-yl)phenyl)-1H-indene-1,3(2H)-dione with various active methylene compounds in ethanol containing sodium acetate at 0-5 °C. The structures of the newly synthesized compounds were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic routes whenever possible. The newly synthesized compounds were evaluated for their antitumor activity against a breast cancer cell line (MCF-7) and a human colon cancer cell line (HCT-116). The results revealed that the tested compounds showed high variation in the inhibitory growth rates and activities against the tested tumor cell lines. All newly synthesized compounds screen towards microorganisms e.g. Gram-negative bacteria, Gram-positive bacteria, and Fungi. Conclusions: 2-(4-(5-Amino-1H-pyrazol-3-yl)phenyl)isoindoline-1,3-dione proved to be a useful precursor for the synthesis of various pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c]-1,2,4- triazines. The structures of the newly synthesized compounds were confirmed by spectral data and elemental analyses. The newly synthesized compounds were tested in vitro against the MCF-7, HCT-116 human cancer cell line and compared with doxorubicin as the standard, using the MTT viability assay. Most of the tested compounds were found to have moderate to high anticancer activity.

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The Bioactive Compound and Mechanism of Action of Sea Cucumber (Holothuridae) as Anticancer: A Review

The Journal of Pure and Applied Chemistry Research ◽

10.21776/ub.jpacr.2020.009.03.534 ◽

2020 ◽

Vol 9 (3) ◽

pp. 153-170

Author(s):

Diah Anggraini Wulandari ◽

◽

Gita Syahputra ◽

Masteria Yunovilsa Putra ◽

◽

...

Keyword(s):

Cell Line ◽

Cancer Cell ◽

Mechanism Of Action ◽

Sea Cucumber ◽

Cancer Cell Line ◽

Bioactive Compound ◽

New Drugs ◽

Sulfated Polysaccharides ◽

Marine Biodiversity ◽

Cancer Drugs

The extreme development and resistance towards cancer drugs, and also the high toxicity, drug resistance and side effects of cancer chemotherapy drug triggers us to develop new drugs as one of the alternative substitutes or combinations of cancer drugs, one of the resources come from marine biodiversity especially sea cucumber. The bioactive compound from sea cucumber can inhibit cancer cell growth with the various mechanism. This study aims to analyze chemical composition, bioactive compound from sea cucumber to inhibit cancer cell line and to analyze mechanism of action of sea cucumber as anticancer with the most recent research studies. The result shows sea cucumber contained protein 44-82%, amino acid, fatty acid, collagen, peptide, micro essential. Each sea cucumber species produced the different secondary metabolites that can use as anticancer. Sea cucumbers contain triterpene glycosides, saponins, holothurin A, stichoposides, frondoside, cucumariosides, dsechinoside, fucoidan, triterpenoid aglycones (philinopgeni), non-glycosaminoglycan, sulfated glycans, sulfated polysaccharides, non-glycosaminosides) that can inhibit cancer cell line. Those bioactive compounds have a various mechanism such as apoptosis in cell line and mitochondria, antioxidative mechanism and membranolytic.

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Synthesis of new analogs of 3-methyl-[1,2,4] triazolo [3,4-a] phthalazines via Suzuki coupling and evaluation of their anticancer and antimicrobial activity

Mediterranean Journal of Chemistry ◽

10.13171/mjc841905257hbb ◽

2019 ◽

Vol 8 (4) ◽

pp. 261-269 ◽

Cited By ~ 2

Author(s):

Gollapudi Ravi Kumar ◽

Chandra Mohan Kurmarayuni ◽

Manideepa Indupalli ◽

Ramya Krishna Pallapati ◽

Hari Babu Bollikolla

Keyword(s):

Antimicrobial Activity ◽

Cell Line ◽

Cancer Cell ◽

Phthalic Anhydride ◽

Cancer Cell Line ◽

Suzuki Coupling ◽

Antimicrobial Activities ◽

Inhibition Activity ◽

Active Compounds ◽

Hct 116

A series of new N-aryl substituted phenyl acetamide analogs of 3-methyl-[1,2,4] triazolo[3,4-a] phthalazines were synthesized starting from commercially available, in-expensive phthalic anhydride in good yields (65-75 %) via Suzuki Coupling. These compounds were tested for inhibition activity against HCT 116 cancer cell line by using MIT assay. Among the library of compounds, N-(3-methoxyphenyl)-2-(4-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)phenyl) acetamide followed by 2-(4-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)phenyl)-N-(m-tolyl) acetamide and Â N-(3-chlorophenyl)-2-(4-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)phenyl) acetamide Â were found to be active compounds with IC50 of 70 to and 90 Âµg mL-1. Further, the compounds were also screened for their antimicrobial activities.

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Phytochemical and Biological Investigation of Ipomoea carnea Jacq. Grown in Egypt

International Journal of Pharmacognosy and Phytochemical Research ◽

10.25258/phyto.v9i2.8074 ◽

2017 ◽

Vol 9 (2) ◽

Author(s):

Amel M Kamal ◽

Zeinab T. Abdel Shakour ◽

Sherif Abdel All ◽

Amany A. Sleem ◽

Eman G. Haggag

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

Antimicrobial Activities ◽

Total Phenolic ◽

Biological Investigation ◽

Ipomoea Carnea ◽

Ethanol Extracts

Total phenolic and flavonoid contents of the leaves and flowers of Ipomoea carnea Jacq. were carried out using Folin-Ciocalteu’s and aluminum chloride assays, respectively. Resulted in 6.59 and 9.37 mg gallic acid equivalent (GAE)/g. dry wt. and 1.336% and 0.885% rutin equivalent (RE)/g for leaves and flowers, respectively. The concentration of rutin and β-sitosterol in leaves and flowers extracts of I. carnea were also estimated by HPLC analysis resulting in 9.174 and 2.733 mg/g dry wt. (rutin) and 0.463, 17.085 mg/g dry wt. (β-sitosterol) for leaves and flowers, respectively. Chromatographic separation of the leaves and flowers ethanol extracts led to the isolation of a new biflavonoid compound: 3ꞌ, 3ꞌꞌꞌꞌ, 5, 5ꞌꞌꞌ, 7, 7ꞌꞌꞌ-O-β-D-glucosyl-4ꞌ, 4ꞌꞌꞌꞌ-biflavonoyl ether [4ꞌ-O-4ꞌꞌꞌꞌ Bis-isoquercetin] (Ipomoeflavoside) from leaves and other four known compounds namely; caffeoyl ethyl ester, caffeic acid, rutin, lycopene isolated for the first time from leaves and β-sitosterol from flowers. The leaves and flowers ethanol extracts showed antioxidant, antihyperglycemic and hepatoprotective activities. They were also evaluated for their anticancer and antimicrobial activities. The ethanol leaves extract showed the highest cytotoxic activity against the breast cancer cell line, with (IC50: 7.4 µg/ml) while it showed weak cytotoxic effect on liver and colon cancer cell lines (IC50:23 and 35 µg/ml) respectively, The ethanol flowers extract showed weak or no anticancer cytotoxic activity against the tested cancer cell lines. The leaves and flowers ethanol extracts showed significant antimicrobial activity against Streptococcus pneumonia, Bacillus subtillis, Escherichia coli and Aspergillus fumigatus while showing no activity against Candida albicans and Pseudomonas aeurginosa.

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