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27 pages, 4491 KiB

Open AccessArticle

An In Vitro Antimicrobial, Anticancer and Antioxidant Activity of N–[(2–Arylmethylthio)phenylsulfonyl]cinnamamide Derivatives

by Anita Bułakowska, Jarosław Sławiński, Rafał Hałasa, Anna Hering, Magdalena Gucwa, J. Renata Ochocka and Justyna Stefanowicz-Hajduk

Molecules 2023, 28(7), 3087; https://doi.org/10.3390/molecules28073087 - 30 Mar 2023

Cited by 6 | Viewed by 1672

Abstract

Cinnamic acid is a plant metabolite with antimicrobial, anticancer, and antioxidant properties. Its synthetic derivatives are often more effective in vitro than parent compounds due to stronger biological activities. In our study, we synthesized ten new N–(4–chloro–2–mercapto–5–methylphenylsulfonyl)cinnamamide derivatives, containing two pharmacophore groups: [...] Read more.

Cinnamic acid is a plant metabolite with antimicrobial, anticancer, and antioxidant properties. Its synthetic derivatives are often more effective in vitro than parent compounds due to stronger biological activities. In our study, we synthesized ten new N–(4–chloro–2–mercapto–5–methylphenylsulfonyl)cinnamamide derivatives, containing two pharmacophore groups: cinnamic acid moiety and benzenesulfonamide. The antimicrobial activity of the obtained compounds was estimated using different types of Gram-positive and Gram-negative bacteria, fungus species of Candida albicans, as well as clinical strains. The compounds were evaluated on biofilm formation and biofilm formed by Staphylococcus clinical strains (methicillin–resistance S. aureus MRSA and methicillin–resistance coagulase–negative Staphylococcus MRCNS). Furthermore, blood bacteriostatic activity test was performed using S. aureus and S. epidermidis. In cytotoxic study, we performed in vitro hemolysis assay on domestic sheep peripheral blood and MTT [3–(4,5–dimethylthiazol–2–yl)–2,5–diphenyltetrazolium bromide] assay on human cervical HeLa, ovarian SKOV-3, and breast MCF-7 cancer cell lines. We also estimated antioxidant activity of ten compounds with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′–azino–bis(3–ethylbenzthiazoline–6–sulfonic acid) (ABTS) assays. Our results showed a significant antimicrobial activity of the compounds. All of them were active on Staphylococcus and Enterococcus species (MIC was 1–4 µg/mL). The compounds 16d and 16e were the most active on staphylococci clinical strains and efficiently inhibited the biofilm formation and biofilm already formed by the clinical staphylococci. Moreover, the hemolytic properties of the tested compounds occurred in higher quantities (>32.5 µg/mL) than the concentrations that inhibited both the growth of bacteria in the blood and the formation and growth of biofilm. The results of MTT assay showed that compounds 16c, 16d, 17a, and 17d demonstrated the best activity on the cancer cells (the IC₅₀ values were below 10 µg/mL). Compound 16f was the least active on the cancer cells (IC₅₀ was > 60 µg/mL). Antiradical tests revealed that compounds 16f and 17d had the strongest antioxidant properties within the tested group (IC₅₀ was 310.50 ± 0.73 and 574.41 ± 1.34 µg/mL in DPPH, respectively, and 597.53 ± 1.3 and 419.18 ± 2.72 µg/mL in ABTS assay, respectively). Our study showed that the obtained cinnamamide derivatives can be used as potential antimicrobial therapeutic agents. Full article

(This article belongs to the Special Issue Antioxidant, Antimicrobical and Anticancer Activity of Natural Product and Their Derivatives)

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12 pages, 2522 KiB

Open AccessArticle

Do Rutin and Quercetin Retain Their Structure and Radical Scavenging Activity after Exposure to Radiation?

by Natalia Rosiak, Judyta Cielecka-Piontek, Robert Skibiński, Kornelia Lewandowska, Waldemar Bednarski and Przemysław Zalewski

Molecules 2023, 28(6), 2713; https://doi.org/10.3390/molecules28062713 - 17 Mar 2023

Cited by 2 | Viewed by 1308

Abstract

The influence of ionizing radiation on the physicochemical properties of quercetin and rutin in the solid state was studied. Quercetin and rutin were irradiated with the standard recommended radiation dose (25 kGy) according to EN 522 standard. The samples were irradiated by electron [...] Read more.

The influence of ionizing radiation on the physicochemical properties of quercetin and rutin in the solid state was studied. Quercetin and rutin were irradiated with the standard recommended radiation dose (25 kGy) according to EN 522 standard. The samples were irradiated by electron beam radiation. EPR studies indicate the formation of a small number of free radicals due to irradiation. Moreover, some radicals recombined with the mean lifetime of 1200 and 93 h, and a stable radical concentration reached only 0.29 and 0.90 ppm for quercetin and rutin, respectively. The performed spectroscopic study (FT-IR) confirmed the radiostability of the flavonoids tested. Chromatographic tests (HPLC, HPLC-MS) showed that irradiation of quercetin and rutin with a 25 kGy dose did not change the physicochemical properties of the tested compounds. Degradation products were not observed. The antioxidant activities were determined by the 2,2-diphenyl-1-pycrylhydrazyl (DPPH) free radical scavenging activity assay, ABTS Radical Scavenging Assay (ABTS), Ferric Reducing Antioxidant Power Assay (FRAP), Cupric Ion Reducing Antioxidant Capacity Assay (CUPRAC). The conducted research confirmed that exposure to ionizing radiation does not change the chemical structure of tested flavonoids and their antioxidant properties. Full article

(This article belongs to the Special Issue Antioxidant, Antimicrobical and Anticancer Activity of Natural Product and Their Derivatives)

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15 pages, 1109 KiB

Open AccessArticle

Anti-Mycobacterial N-(2-Arylethyl)quinolin-3-amines Inspired by Marine Sponge-Derived Alkaloid

by Junya Mukomura, Hiroki Nonaka, Hiromasa Sato, Maho Kishimoto, Masayoshi Arai and Naoyuki Kotoku

Molecules 2022, 27(24), 8701; https://doi.org/10.3390/molecules27248701 - 08 Dec 2022

Viewed by 1573

Abstract

The synthesis and evaluation of simplified analogs of marine sponge-derived alkaloid 3-(phenethylamino)demethyl(oxy)aaptamine were performed to develop novel anti-mycobacterial substances. Ring truncation of the tricyclic benzo[de][1,6]-naphthyridine skeleton effectively weakened the cytotoxicity of the natural product, and the resulting AC-ring analog exhibited good [...] Read more.

The synthesis and evaluation of simplified analogs of marine sponge-derived alkaloid 3-(phenethylamino)demethyl(oxy)aaptamine were performed to develop novel anti-mycobacterial substances. Ring truncation of the tricyclic benzo[de][1,6]-naphthyridine skeleton effectively weakened the cytotoxicity of the natural product, and the resulting AC-ring analog exhibited good anti-mycobacterial activity. A structure–activity relationship (SAR) study, synthesizing and evaluating some analogs, demonstrated the specificity and importance of the N-(2-arylethyl)quinolin-3-amine skeleton as a promising scaffold for anti-mycobacterial lead compounds. Full article

(This article belongs to the Special Issue Antioxidant, Antimicrobical and Anticancer Activity of Natural Product and Their Derivatives)

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18 pages, 4734 KiB

Open AccessArticle

Yamogenin-Induced Cell Cycle Arrest, Oxidative Stress, and Apoptosis in Human Ovarian Cancer Cell Line

by Justyna Stefanowicz-Hajduk, Anna Hering, Magdalena Gucwa, Monika Czerwińska and J. Renata Ochocka

Molecules 2022, 27(23), 8181; https://doi.org/10.3390/molecules27238181 - 24 Nov 2022

Cited by 1 | Viewed by 1521

Abstract

Steroidal saponins are a group of compounds with complex structures and biological activities. They have anti-inflammatory, antimicrobial, fungicidal, and antitumor properties. Yamogenin is one of the spirostane saponins and occurs in Trigonella foenum-graecum, Asparagus officinalis, and Dioscorea collettii. It is [...] Read more.

Steroidal saponins are a group of compounds with complex structures and biological activities. They have anti-inflammatory, antimicrobial, fungicidal, and antitumor properties. Yamogenin is one of the spirostane saponins and occurs in Trigonella foenum-graecum, Asparagus officinalis, and Dioscorea collettii. It is a stereoisomer of diosgenin—a well-known compound whose activity and mechanisms of action in cancer cells are determined. However, the antitumor effect of yamogenin is still little known, and the mechanism of action has not been determined. In this study, we evaluated the effect of yamogenin on human ovarian cancer SKOV-3 cells in vitro by determining the cellular factors that trigger cell death. The viability of the cells was assessed with a Real-Time xCELLigence system and the cell cycle arrest with flow cytometry. The activity of initiator and executioner caspases (-8, -9, and -3/7) was estimated with luminometry and flow cytometry, respectively. The mitochondrial membrane depolarization, the level of oxidative stress, and DNA damage in the yamogenin-treated cells were also evaluated by flow cytometry. Genes expression analysis at the mRNA level was conducted with Real-Time PCR. Bid activation and chromatin condensation were estimated with fluorescent microscopy. The obtained results indicate that yamogenin has cytotoxic activity in SKOV-3 cells with an IC₅₀ value of 23.90 ± 1.48 µg/mL and strongly inhibits the cell cycle in the sub-G1 phase. The compound also triggers cell death with a significant decrease in mitochondrial membrane potential, an increase in the level of oxidative stress (over two times higher in comparison to the control), and activation of caspase-8, -9, -3/7, as well as Bid. The results of genes expression indicate that the Tumor Necrosis Factor (TNF) Receptor Superfamily Members (TNF, TNFRSF10, TNFRSF10B, TNFRSF1B, and TNFRSF25), Fas Associated via Death Domain (FADD), and Death Effector Domain Containing 2 (DEDD2) were significantly upregulated and their relative expression was at least two times higher than in the control. Our work shows that yamogenin induces apoptosis in ovarian cancer cells, and both the extrinsic and mitochondrial—intrinsic pathways are involved in this process. Full article

(This article belongs to the Special Issue Antioxidant, Antimicrobical and Anticancer Activity of Natural Product and Their Derivatives)

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12 pages, 2904 KiB

Open AccessArticle

Nardoguaianone L Isolated from Nardostachys jatamansi Improved the Effect of Gemcitabine Chemotherapy via Regulating AGE Signaling Pathway in SW1990 Cells

by Yi-Dan Zheng, Li-Mei Ma, Jin-Jian Lu, Tian Chai, Mohammad Reza Naghavi, Jun-Yi Ma, Chun-Yan Sang and Jun-Li Yang

Molecules 2022, 27(20), 6849; https://doi.org/10.3390/molecules27206849 - 13 Oct 2022

Cited by 3 | Viewed by 1489

Abstract

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide and is known as “the king of cancers”. Currently, gemcitabine (GEM) as the clinical drug of choice for chemotherapy of advanced pancreatic cancer has poor drug sensitivity and ineffective chemotherapy. Nardoguaianone L [...] Read more.

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide and is known as “the king of cancers”. Currently, gemcitabine (GEM) as the clinical drug of choice for chemotherapy of advanced pancreatic cancer has poor drug sensitivity and ineffective chemotherapy. Nardoguaianone L (G-6) is a novel guaiane-type sesquiterpenoid isolated from Nardostachys jatamansi DC., and it exhibits anti-tumor activity. Based on the newly discovered G-6 with anti-pancreatic cancer activity in our laboratory, this paper aimed to evaluate the potential value of the combination of G-6 and GEM in SW1990 cells, including cell viability, cell apoptosis, colony assay and tandem mass tags (TMT) marker-based proteomic technology. These results showed that G-6 combined with GEM significantly inhibited cell viability, and the effect was more obvious than that with single drug. In addition, the use of TMT marker-based proteomic technology demonstrated that the AGE-RAGE signaling pathway was activated after medication-combination. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays were used to validate the proteomic results. Finally, apoptosis was detected by flow cytometry. In conclusion, G-6 combined with GEM induced an increase in ROS level and a decrease in MMP in SW1990 cells through the AGE-RAGE signaling pathway, ultimately leading to apoptosis. G-6 improved the effect of GEM chemotherapy and may be used as a potential combination therapy for pancreatic cancer. Full article

(This article belongs to the Special Issue Antioxidant, Antimicrobical and Anticancer Activity of Natural Product and Their Derivatives)

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Review

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23 pages, 5349 KiB

Open AccessReview

Between the Devil and the Deep Blue Sea—Resveratrol, Sulfotransferases and Sulfatases—A Long and Turbulent Journey from Intestinal Absorption to Target Cells

by Izabela Szymkowiak, Malgorzata Kucinska and Marek Murias

Molecules 2023, 28(8), 3297; https://doi.org/10.3390/molecules28083297 - 07 Apr 2023

Cited by 2 | Viewed by 2081

Abstract

For nearly 30 years, resveratrol has attracted the scientific community’s interest. This has happened thanks to the so-called French paradox, that is, the paradoxically low mortality from cardiovascular causes in the French population despite a diet rich in saturated fat. This phenomenon has [...] Read more.

For nearly 30 years, resveratrol has attracted the scientific community’s interest. This has happened thanks to the so-called French paradox, that is, the paradoxically low mortality from cardiovascular causes in the French population despite a diet rich in saturated fat. This phenomenon has been linked to the consumption of red wine, which contains a relatively high level of resveratrol. Currently, resveratrol is valued for its versatile, beneficial properties. Apart from its anti-atherosclerotic activity, resveratrol’s antioxidant and antitumor properties deserve attention. It was shown that resveratrol inhibits tumour growth at all three stages: initiation, promotion, and progression. Moreover, resveratrol delays the ageing process and has anti-inflammatory, antiviral, antibacterial, and phytoestrogenic properties. These favorable biological properties have been demonstrated in vitro and in vivo in animal and human models. Since the beginning of the research on resveratrol, its low bioavailability, mainly due to its rapid metabolism, especially the first-pass effect that leaves almost no free resveratrol in the peripheral circulation, has been indicated as a drawback that has hindered its use. The elucidation of such issues as pharmacokinetics, stability, and the biological activity of resveratrol metabolites is therefore crucial for understanding the biological activity of resveratrol. Second-phase metabolism enzymes are mainly involved in RSV metabolism, e.g., UDP-glucuronyl transferases and sulfotransferases. In the present paper, we took a closer look at the available data on the activity of resveratrol sulfate metabolites and the role of sulfatases in releasing active resveratrol in target cells. Full article

(This article belongs to the Special Issue Antioxidant, Antimicrobical and Anticancer Activity of Natural Product and Their Derivatives)

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47 pages, 9721 KiB

Open AccessReview

Modified Curcumins as Potential Drug Candidates for Breast Cancer: An Overview

by Abigail L. Flint, David W. Hansen, LaVauria D. Brown, Laura E. Stewart, Eduardo Ortiz and Siva S. Panda

Molecules 2022, 27(24), 8891; https://doi.org/10.3390/molecules27248891 - 14 Dec 2022

Cited by 5 | Viewed by 2274

Abstract

Breast cancer (BC), the most common malignancy in women, results from significant alterations in genetic and epigenetic mechanisms that alter multiple signaling pathways in growth and malignant progression, leading to limited long-term survival. Current studies with numerous drug therapies have shown that BC [...] Read more.

Breast cancer (BC), the most common malignancy in women, results from significant alterations in genetic and epigenetic mechanisms that alter multiple signaling pathways in growth and malignant progression, leading to limited long-term survival. Current studies with numerous drug therapies have shown that BC is a complex disease with tumor heterogeneity, rapidity, and dynamics of the tumor microenvironment that result in resistance to existing therapy. Targeting a single cell-signaling pathway is unlikely to treat or prevent BC. Curcumin (a natural yellow pigment), the principal ingredient in the spice turmeric, is well-documented for its diverse pharmacological properties including anti-cancer activity. However, its clinical application has been limited because of its low solubility, stability, and bioavailability. To overcome the limitation of curcumin, several modified curcumin conjugates and curcumin mimics were developed and studied for their anti-cancer properties. In this review, we have focused on the application of curcumin mimics and their conjugates for breast cancer. Full article

(This article belongs to the Special Issue Antioxidant, Antimicrobical and Anticancer Activity of Natural Product and Their Derivatives)

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54 pages, 23316 KiB

Open AccessReview

Review on Compounds Isolated from Eriocaulaceae Family and Evaluation of Biological Activities by Machine Learning

by Laysa Lanes Pereira Ferreira Moreira, Renata Priscila Barros de Menezes, Luciana Scotti, Marcus Tullius Scotti, Valdemar Lacerda Júnior and Warley de Souza Borges

Molecules 2022, 27(21), 7186; https://doi.org/10.3390/molecules27217186 - 24 Oct 2022

Viewed by 1613

Abstract

Eriocaulaceae is a pantropical family whose main center of biodiversity is in Brazil. In general, the family has about 1200 species, in which phytochemical and biological studies have shown a variety of structures and activities. The aim of this research is to compile [...] Read more.

Eriocaulaceae is a pantropical family whose main center of biodiversity is in Brazil. In general, the family has about 1200 species, in which phytochemical and biological studies have shown a variety of structures and activities. The aim of this research is to compile the compounds isolated in the Eriocaulaceae family and carry out a computational study on their biological targets. The bibliographic research was carried out on six databases. Tables were built and organized according to the chemical class. In addition, a summary of the methods of isolating the compounds was also made. In the computational study were used ChEMBL platform, DRAGON 7.0, and the KNIME 4.4.0 software. Two hundred and twenty-two different compounds have been isolated in sixty-eight species, divided mainly into flavonoids and naphthopyranones, and minor compounds. The ligand-based virtual screening found promising molecules and molecules with multitarget potential, such as xanthones 194, 196, 200 and saponin 202, with xanthone 194 as the most promising. Several compounds with biological activities were isolated in the family, but the chemical profiles of many species are still unknown. The selected structures are a starting point for further studies to develop new antiparasitic and antiviral compounds based on natural products. Full article

(This article belongs to the Special Issue Antioxidant, Antimicrobical and Anticancer Activity of Natural Product and Their Derivatives)

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