scholarly journals Discovery of Novel Polycyclic Polyprenylated Acylphloroglucinols from the Fruits of Garcinia xanthochymus as Antitumor Agents by Suppressing the STAT3 Signaling

2021 ◽  
Vol 22 (19) ◽  
pp. 10365
Author(s):  
Shan Jin ◽  
Wen Wang ◽  
Fei Gan ◽  
Wenli Xie ◽  
Jing Xu ◽  
...  
Keyword(s):  
Proliferative Activity ◽  
Antitumor Agents ◽  
Biological Activities ◽  
Human Tumor ◽  
Sh2 Domain ◽  
Effector Proteins ◽  
Oncogenic Signaling ◽  
Garcinia Xanthochymus ◽  
Ic50 Values ◽  
Mcf 7

Pharmacologic studies have revealed that polycyclic polyprenylated acylphloroglucinols (PPAPs) collectively exhibit a broad range of biological activities, including antineoplastic potential. Here, six new PPAPs, named garcixanthochymones F–K (3, 5, 7, 8, 11, and 15), together with nine known analogues were isolated from the fruits of Garcinia xanthochymus. Their structures were elucidated based on the spectroscopic data, including UV, HRESIMS, and NMR, and quantum chemical calculations. All the isolated PPAPs were tested for anti-proliferative activity against four human tumor cell lines, including SGC7901, A549, HepG2, and MCF-7. Most of the PPAPs possessed high anti-proliferative activity with IC50 values in the range of 0.89 to 36.98 μM, and significant apoptosis was observed in MCF-7 cells exposed to compounds 2 and 5. Besides, docking results showed that compounds 2 and 5 could strongly combine with the Src homology 2 (SH2) domain of STAT3 via hydrogen bond and hydrophobic interaction, which is one of the key oncogenes and crucial therapeutic targets. Furthermore, compounds 2 and 5 efficiently downregulated the expression of p-STAT3Tyr705 and pivotal effector proteins involved in oncogenic signaling pathways of MCF-7 cells.

scholarly journals Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3041
Author(s):  
Xiaohan Hu ◽  
Sheng Tang ◽  
Feiyi Yang ◽  
Pengwu Zheng ◽  
Shan Xu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Design Synthesis ◽  
Structure Activity ◽  
Excellent Activity ◽  
Ic50 Values ◽  
Mcf 7

Two series of olmutinib derivatives containing an acrylamide moiety were designed and synthesized, and their IC50 values against cancer cell lines (A549, H1975, NCI-H460, LO2, and MCF-7) were evaluated. Most of the compounds exhibited moderate cytotoxic activity against the five cancer cell lines. The most promising compound, H10, showed not only excellent activity against EGFR kinase but also positive biological activity against PI3K kinase. The structure–activity relationship (SAR) suggested that the introduction of dimethylamine scaffolds with smaller spatial structures was more favorable for antitumor activity. Additionally, the substitution of different acrylamide side chains had different effects on the activity of compounds. Generally, compounds H7 and H10 were confirmed as promising antitumor agents.

scholarly journals Labdane and Abietane Diterpenoids from Juniperus oblonga and Their Cytotoxic Activity

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1561 ◽  
Author(s):  
Qiao ◽  
Khutsishvili ◽  
Alizade ◽  
Atha ◽  
Borris
Keyword(s):  
Cell Lines ◽  
Human Tumor ◽  
2D Nmr ◽  
Human Tumor Cell Lines ◽  
Abietane Diterpenoids ◽  
Whole Plant ◽  
Phytochemical Investigation ◽  
Ic50 Values ◽  
First Time ◽  
Mcf 7

A phytochemical investigation of the whole plant of Juniperus oblonga led to the isolationof one previously undescribed labdane diterpenoid, (4R,5S,9S,10R)‐13‐des‐ethyl‐13‐oxolabda‐8(17),11E‐dien‐19‐oic acid (1), together with nine known diterpenoids (2–3, 6–12), two lignans (4, 5),and a coumarin (13). The structures of all the compounds were elucidated on the basis ofspectrometric data, primarily one‐dimensional (1D)‐ and two‐dimensional (2D)‐NMR and massspectrometry. Electronic circular dichroism (ECD) calculations determined the absoluteconfiguration of 1. In addition, the isolated compounds were evaluated for their cytotoxic activityagainst three human tumor cell lines (HepG2, MCF‐7, and HeLa). 6,12‐Dihydroxyabieta‐5,8,11,13‐tetraen‐7‐one (6) showed moderate cytotoxicity against all three cell lines with IC50 values rangingfrom 24.41 μM to 58.39 μM and trilobinone (10) showed weaker activity with IC50 values rangingfrom 56.93 μM to 79.98 μM. None of the isolated diterpenoids have been previously reported fromJuniperus oblonga, and five compounds are here reported from the genus Juniperus for the first time.

Antioxidant, cytotoxic activity and pharmacokinetic studies by SwissAdme, Molinspiration, Osiris and DFT of PhTAD-substituted dihydropyrrole derivatives

2021 ◽  
Vol 17 ◽  
Author(s):  
Arif Ayar ◽  
Masuk Aksahin ◽  
Seda Mesci ◽  
Burak Yazgan ◽  
Melek Gül ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Heterocyclic Compounds ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Molecular Structures ◽  
Biologically Active ◽  
Pharmacokinetic Studies ◽  
Ic50 Values ◽  
Mcf 7

Background: Pyrrole compounds having a heterocyclic structure are the most researched and biological activities such as antioxidant and anticancer. Objective: Herein is a first effort to study the significance of heterocyclic compounds to include pyrrole and triazolidine-3,5-dion moiety, on the pharmacokinetic, antioxidant activity and cytotoxic activity on MCF-7 and MCF-12A cell lines. Method: The molecular structures of compounds I-XIV were simulated by the theoretical B3LYP/DFT method. Pharmacokinetic studies of PhTAD-substituted heterocyclic compounds (I-XIV) were analyzed to show Lipinski's rules via in-silico methods of Swiss-ADME. The drug likeness calculations were carried out Molinspiration analyses. The some toxicity risk parameter can be quantified using Osiris. Antioxidant activities determined by DPPH, Fe+2 ions chelating and reducing. Cytotoxic activity measured by MTT and RTCA. Results: Compared with the DPPH activity, the metal chelating activity exhibited serious similar antioxidant effects by PhTAD substituted pyrrole compounds. The same compounds showed the highest activity among the two antioxidant activities. The IC50 values of the compounds are in the range of 12 and 290 µM in MCF-7 cell line. In the MTT and RTCA assays, All compounds showed cytotoxic activity, but about half of the fourteen compounds showed high cytotoxicity. IC50 values of the compounds are in the range of 5 and 54 µM for MTT and range of 1.5 and 44 µM for RTCA. Conclusion: Data of the antioxidant and cytotoxic activity of PhTAD-substituted dihydropyrrole-derived compounds in MCF-7 and MCF-12A cell lines confirmed that the compounds are a biologically active compound and is notable for anti-cancer researches.

scholarly journals Juncaceae Species as Promising Sources of Phenanthrenes: Antiproliferative Compounds from Juncus maritimus Lam

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 999
Author(s):  
Norbert Kúsz ◽  
Dóra Stefkó ◽  
Anita Barta ◽  
Annamária Kincses ◽  
Nikoletta Szemerédi ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Human Tumor ◽  
Biologically Active ◽  
Human Tumor Cell Lines ◽  
Ring Compounds ◽  
Diphenyltetrazolium Bromide ◽  
Juncus Maritimus ◽  
Ic50 Values ◽  
Vinyl Group ◽  
Mcf 7

Juncaceae family represents an abundant source of phenanthrenes. In continuation of our work aiming at the isolation of biologically active compounds from Juncaceae species, Juncus maritimus Lam. was subjected to phytochemical and pharmacological investigations. The isolation process was carried out by using combined extraction and chromatographic methods. The structures of the obtained chemical compounds were elucidated by spectroscopic analysis, including HRESIMS, 1D (1H, 13C-JMOD), and 2D (1H-1H-COSY, HSQC, HMBC, NOESY) NMR spectra. Four new [maritins A–D (1–4)] and seven known phenanthrenes (5–11) were isolated from the plant, of which two (4 and 11) are phenanthrene dimers composed of effusol monomers. Maritin C (3) has an unusual 4,5-ethanophenanthrene skeleton most likely produced by biosynthetic incorporation of a vinyl group into a cyclohexadiene ring. Compounds 1–11 were tested for their antiproliferative activity on seven human tumor cell lines (HeLa, HTM-26, T-47D, A2780, A2780cis, MCF-7, KCR) and one normal cell line (MRC-5) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The dimeric phenanthrenes showed strong antiproliferative activity against T-47D cells with IC50 values of 9.1 and 6.2 µM, respectively.

scholarly journals Essential oil composition and cytotoxic activity in two species of the plant genus Vismia (Hypericaceae) from the Venezuelan Andes

2020 ◽  
Vol 68 (3) ◽  
Author(s):  
Janne Rojas Vera ◽  
Alexis Buitrago Díaz ◽  
Francisco A. Arvelo ◽  
Felipe J. Sojo ◽  
Alírica I. Suarez ◽  
...  
Keyword(s):  
Essential Oil ◽  
Essential Oils ◽  
Cytotoxic Activity ◽  
Tumor Cells ◽  
Biological Activities ◽  
Human Tumor ◽  
Essential Oil Composition ◽  
Gas Chromatography Mass Spectrometry ◽  
Oil Composition ◽  
Mcf 7

Abstract. Introduction: The Vismia genus belongs to the Hypericaceae family and comprises around 57 species of which 17 have been located in Venezuela. Previous investigations have been carried out in extracts as well as pure isolated compounds, revealing antimicrobial, antioxidant and anti-HIV, among other, biological activities. Objective: This investigation aims to determine the cytotoxic activity of essential oils from leaves of Vismia baccifera Triana & Planch (VBJ and VBV) and Vismia macrophylla Kunth (VM) collected in three different locations of the Venezuelan Andean region. Methods: Essential oils obtained by hydrodistillation were analyzed using gas chromatography-mass spectrometry (GC-MS) and their cytotoxic activity was analyzed following the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Human tumor cell lines from SKBr3, MCF-7 and PANC-1, two breast carcinomas and one pancreatic adenocarcinoma of ductal type, were tested with the oil samples and human dermis fibroblasts were used as non-tumor cells. Results: β-caryophyllene and trans-caryophyllene were present as major components in VBJ and VBV, respectively, while γ-bisabolene was the main component in the VM sample. Anticancer activity was observed on V. baccifera essential oil against SKBr3, MCF-7 and PANC-1. The selectivity index showed that VBV is highly selective against the SKBr3 cell line and has no activity against non-tumor cells. Conclusions: These results are considered a contribution to natural products research and may provide supportive data for future studies on cancer.

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

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.

scholarly journals New Heterocyclic Combretastatin A-4 Analogs: Synthesis and Biological Activity of Styryl-2(3H)-Benzothiazolones

2021 ◽  
Vol 14 (12) ◽  
pp. 1331
Author(s):  
Gjorgji Atanasov ◽  
Rusi I. Rusew ◽  
Vladimir M. Gelev ◽  
Christo D. Chanev ◽  
Rosica Nikolova ◽  
...  
Keyword(s):  
Cell Death ◽  
Biological Activities ◽  
Cycle Phase ◽  
Cytotoxic Activities ◽  
Drug Induced ◽  
Combretastatin A4 ◽  
Ic50 Values ◽  
Ea.Hy926 Cells ◽  
Ht 29 ◽  
Mcf 7

Here, we describe the synthesis, characterization, and biological activities of a series of 26 new styryl-2(3H)-benzothiazolone analogs of combretastatin-A4 (CA-4). The cytotoxic activities of these compounds were tested in several cell lines (EA.hy926, A549, BEAS-2B, MDA-MB-231, HT-29, MCF-7, and MCF-10A), and the relations between structure and cytotoxicity are discussed. From the series, compound (Z)-3-methyl-6-(3,4,5-trimethoxystyryl)-2(3H)-benzothiazolone (26Z) exhibits the most potent cytotoxic activity (IC50 0.13 ± 0.01 µM) against EA.hy926 cells. 26Z not only inhibits vasculogenesis but also disrupts pre-existing vasculature. 26Z is a microtubule-modulating agent and inhibits a spectrum of angiogenic events in EA.hy926 cells by interfering with endothelial cell invasion, migration, and proliferation. 26Z also shows anti-proliferative activity in CA-4 resistant cells with the following IC50 values: HT-29 (0.008 ± 0.001 µM), MDA-MB-231 (1.35 ± 0.42 µM), and MCF-7 (2.42 ± 0.48 µM). Cell-cycle phase-specific experiments show that 26Z treatment results in G2/M arrest and mitotic spindle multipolarity, suggesting that drug-induced centrosome amplification could promote cell death. Some 26Z-treated adherent cells undergo aberrant cytokinesis, resulting in aneuploidy that perhaps contributes to drug-induced cell death. These data indicate that spindle multipolarity induction by 26Z has an exciting chemotherapeutic potential that merits further investigation.

scholarly journals Bioactivities of essential oils from different parts of Spiranthera odoratissima (Rutaceae)

Rodriguésia ◽  
2020 ◽  
Vol 71 ◽  
Author(s):  
Fernando Duarte Cabral ◽  
Cassia Cristina Fernandes ◽  
Arthur Barcelos Ribeiro ◽  
Iara Squarisi Squarisi ◽  
Denise Crispim Tavares ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Normal Cell ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Ic50 Values ◽  
Mcf 7

Abstract This paper aims to investigate, for the first time, in vitro antitubercular, antileishmanial and antiproliferative activities of essential oils (EOs) from S. odoratissima leaves and flowers - grown in midwestern Brazil - against Mycobacterium tuberculosis, promastigote forms of Leishmania amazonensis and human tumor cell lines. Antimycobacterial activity of EOs was evaluated in terms of the minimal inhibitory concentration (MIC). EOs from leaves and flowers showed to be active antimicrobials against M. tuberculosis, since MIC values were 150 µg/mL and 162.5 µg/mL, respectively. Both EOs exhibited significant activity against promastigote forms of L. amazonensis; IC50 values (50% growth inhibition) were 14.36 ± 2.02 (EOs from leaves) and 19.89 ± 2.66 µg/mL (EOs from flowers). Antiproliferative activity in normal (GM07492A, lung fibroblasts) and tumor (MCF-7, HeLa and M059J) cell lines was performed by the XTT assay; results were expressed as IC50 (50% cell growth inhibition) and the selective index was calculated. IC50 values of EOs from leaves and flowers obtained in normal cell lines for were 502.97 ± 40.33 µg/mL and 370.60 ± 2.01 µg/mL, respectively. Antiproliferative activity was observed against human tumor cell lines, whose IC50 values were significantly lower than those obtained in normal cell lines of MCF-7 cells (367.57 ± 4.46 µg/mL-EOs from leaves and 357.70 ± 1.85 µg/mL-EOs from flowers) and M059J cells (492.53 ± 56.67 µg/mL-EOs from leaves and 324.90 ± 6.72 µg/mL-EOs from flowers), thus, indicating selectivity. These in vitro results showed that EOs from S. odoratissima may be an antimycobacterial, antiparasitic and antitumor agent.

Synthesis of thiazolyl-N-phenylmorpholine derivatives and their biological activities

2020 ◽  
Vol 16 ◽  
Author(s):  
Amerah M. Al-Soliemy ◽  
Thoraya A. Farghaly ◽  
Eman M. H. Abbas ◽  
Mohamed R. Shaaban ◽  
Mohie E. M. Zayed ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cells ◽  
Antitumor Agents ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Thiazole Derivatives ◽  
Design And Synthesis ◽  
Good Potential ◽  
Potent Growth ◽  
Mcf 7

Background: Morpholine and thiazole rings are two heterocycles which well-known with wide spectrum of different biological activities especially antitumor activity. Objective: The aim of the work is to design and synthesis hybrid heterocyclic compounds of morpholine and thiazole moieties via the reaction of morpholino-thiosemicarbazone derivatives with various αhalocarbonyl compounds and screening their antitumor activity against three tumor cell lines namely, TK-10, MCF-7 and UACC-62. Method: An efficient synthesis of a series of Nphenylmorpholine derivatives linked with thiazole moiety were accomplished. The reaction of Nsubistituted-2-(N-phenylmorpholine)ethylidene)hydrazine-1-carbothioamide (thiosemicarbazone derivative) with acetyl and ester-hydrazonoyl chlorides, α-chloroketones, or α-bromoesters afforded the corresponding thiazole derivatives pendent to N-phenylmorpholine moiety in good to excellent yields. Result: Mass, 1 H NMR, 13C NMR, and elemental analysis were used to confirm the structure of all the new derivatives. The antitumor activities of synthesized Nphenylmorpholine-thiazole derivatives were investigated against three tumor cells namely, TK-10, MCF-7 and UACC-62. The results of such investigation indicated that some derivatives showed good potential to inhibit the growth of the two cells of the tested tumor cells. Surprise, one of the tested compounds, N-methyl thiosemicarbazone derivative 7 revealed potent growth inhibition of all the three tumor cells. Conclusion: We have succeeded to synthesize a series of Nphenylmorpholine derivatives pendant to thiazole moiety as antitumor agents.

Synthesis and Antitumor Evaluation of Novel N-substituted Norcantharidin Imidazolium Derivatives

2018 ◽  
Vol 15 (2) ◽  
pp. 237-245 ◽  
Author(s):  
Rong-Rong Sun ◽  
Jia-Hui Guo ◽  
Cui Yang ◽  
Li-Juan Yang ◽  
Chao Huang
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Antitumor Agents ◽  
Human Tumor ◽  
Imidazole Ring ◽  
Electronic Effects ◽  
Imidazolium Salt ◽  
Ic50 Values ◽  
Human Lung Carcinoma

Aims and Objectives: Cantharidin is a terpenoid with a high vesicant potency isolated from Mylabris caraganae and various other insects, which originates from the Chinese traditional medicine and has a long history of use as antiproliferative agent. Modified cantharidin derivatives are researched for retainable antitumor activities and lower toxicity. And imidazolium salt is an important building block in drug discovery with pharmacological activities. This study was undertaken to identify that N-substituted norcantharidin imidazolium derivatives possess potential bioactivity. Materials and Method: Using readily available furan, maleic anhydride and imidazoles as starting materials, a series of novel N-substituted norcantharidin imidazolium derivatives have been designed and synthesized. The cytotoxic potential of all newly synthesized N-substituted norcantharidin imidazolium derivatives was assessed in vitro against a panel of human tumor cell lines, Human epidermal carcinoma, human lung carcinoma, liver hepatocellular carcinoma, pheochromocytoma of the rat adrenal medulla. Results: The imidazolium derivatives 6a-6f and 6m-6o, bearing a 5,6-dibromohexahydro-4,7-epoxyisobenzofuran- 1,3-dione or 5-bromo-7-oxabicyclo[2.2.1]hepta- 2,5-diene-2,3-dicarboxylate and electron-donating group, carbonyl and propenyl substituent at position-1 of the imidazole ring, were found to be the most potent compounds as antitumor agents. Notably, compounds 6m and 6n exhibited cytotoxic activity selectively against Hela and A549 cell lines with IC50 values 1.38-fold, 5.04-fold, lower than DDP, while compound 6f showed powerful inhibitory activities selectively against Hela and PC12 cell lines. Conclusion: Steric and electronic effects have an important role in determining the cytotoxic activity of imidazolium salts. The norcantharidin-imidazole 6f, 6m, 6n and 6o can be considered to be promising leads for further structural modifications guided by the valuable information derivable.

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