Article
Agriculture, Multidisciplinary
Charles L. Cantrell, Maria Lucia Travaini, Joanna Bajsa-Hirschel, Lara D. Svendsen, Amber Reichley, Gustavo M. Sosa, Seong Jong Kim, Prabin Tamang, Kumudini Meepagala, Stephen O. Duke
Summary: In this study, the effect of O-alkylation and O-arylalkylation on the herbicidal and antifungal activity of khellin and visnagin analogues was examined. The results showed that O-demethyl butylated visnagin analogue exhibited the highest herbicidal activity, while O-demethyl ethylated analogues of khellin and visnagin showed good antifungal activity.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Karolina Dzedulionyte, Nina Fuxreiter, Ekaterina Schreiber-Brynzak, Asta Zukauskaite, Algirdas Sackus, Verena Pichler, Egle Arbaciauskiene
Summary: A library of pyrazole-based lamellarin O analogues was synthesized via modification of easily accessible 3(5)-aryl-1H-pyrazole-5(3)-carboxylates using bromination, N-alkylation, and Pd-catalysed Suzuki cross-coupling reactions. The synthesized compounds were evaluated for their physicochemical properties and cytotoxicity against colorectal cancer cell lines. The most active compounds exhibited cell proliferation inhibition in the low micromolar range and triggered cell death through G2/M-phase arrest.
Article
Biochemistry & Molecular Biology
Pei-Fang Chiu, I-Chun Lin, Yeh-Lin Lu, Chiao-Nien Chang, Hui-Yu Chan, Tzung-Shen Lin, Keng-Chang Tsai, Yves S. Y. Hsieh, Mei-Jou Chen, Mei-Hsiang Lin, Pi-Hui Liang
Summary: Inhibition of steroid sulfatase (STS) can decrease estrogen production, thereby suppressing tumor proliferation. In this study, twenty-one tricyclic and tetraheterocyclic coumarin-based derivatives were explored and evaluated for their STS enzyme kinetic parameters, docking models, and cytotoxicity towards breast cancer and normal cells. The tricyclic derivative 9e and tetracyclic derivative 10c were found to be the most promising irreversible inhibitors, with K-I values of 0.05 and 0.4 nM, and k(inact)/K-I ratios of 28.6 and 19.1 nM(-1)min(-1) on human placenta STS, respectively.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Xueying Wang, Jiling Feng, Rong Wu, Jiaqi Tan, Qing Huang, Yeelin Phang, Li Zhang, Wenwei Fu, Hongxi Xu, Changwu Zheng
Summary: This research aims to thoroughly evaluate the potential of Garcinol and its analogues in terms of synthesis, structural diversity, biosynthesis, and prevention of carcinoma cell proliferation. Garcinopicrobenzophenone and eugeniaphenone were synthesized and their structures were clarified. The synthesis also proposed a possible biogenetic synthesis pathway. The cytotoxicity and mechanism of action of the polyisoprenylated benzophenones were studied, showing potential as chemotherapeutic agents in pancreatic cancer cells.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Anqi Du, Na Li, Zhilu Li, Ruowu Shen, Nan Li, Yu Zhou
Summary: Ghrelin and its receptor GHS-R1a regulate synaptic function of hippocampal neurons, potentially impacting memory formation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Chemistry, Medicinal
Kevin Daly, Killian O'Sullivan, Timothy P. O'Sullivan
Summary: The structural modifications and activity relationships of resolvins, protectins, maresins, and their analogues, which are molecules involved in inflammation resolution, are currently being intensively investigated.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Tingting Zhang, Tengyuan Liu, Bassem A. Hassan
Summary: The study presents a detailed protocol for long-term generation of Pax6+ granule cells and Calbindin+ Purkinje cells from embryonic cerebellar progenitors in vitro. The protocol includes dissecting mouse cerebellar anlage, cell seeding, and labeling of progenitor cells for time-lapse video recording of clonal expansion and neuronal differentiation.
Review
Chemistry, Medicinal
Pankaj S. Girase, Sanjeev Dhawan, Vishal Kumar, Suraj R. Shinde, Mahesh B. Palkar, Rajshekhar Karpoormath
Summary: Piperazine, a nitrogen-containing heterocyclic compound, is widely used in medicinal chemistry for its diverse pharmacological activities, particularly in the development of anti-TB molecules. Studies have shown that molecules containing piperazine subunits exhibit potential activity against drug-resistant strains of Mycobacterium tuberculosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Daniela G. G. Dengler, Kaleeckal G. G. Harikumar, Alice Yen, Eduard A. A. Sergienko, Laurence J. J. Miller
Summary: In an effort to develop a drug for obesity, researchers performed a high throughput screening of small molecules to find candidates that can enhance the action of CCK. The study focused on a specific scaffold of tetracyclic molecules and expanded it with commercially available analogs, eliminating off-target effects while retaining its activity as a positive allosteric modulator of CCK1R. These findings provide valuable insights for the future development of potential therapeutic candidates.
Article
Chemistry, Medicinal
Yitian Zhao, Yuan Xiong, Sanfeng Dong, Xiaoqing Guan, Yunqing Song, Yanqing Yang, Kun Zou, Zhao Li, Yong Zhang, Shengquan Fang, Bo Li, Weiliang Zhu, Kaixian Chen, Qi Jia, Guangbo Ge
Summary: A new compound was found to exhibit strong inhibitory effects on human carboxylesterase 2A (hCES2A), with better activity in living cells, which may have important implications for drug metabolism. Molecular docking simulations demonstrated that these compounds can act as mixed inhibitors with good specificity and inhibitory potency.
Review
Plant Sciences
Hannah J. Denison, Sianne L. Schwikkard, Mouhamad Khoder, Alison F. Kelly
Summary: Antimicrobial resistance is a global challenge, and natural products like curcumin and its analogues have shown potential antibacterial activity. This review provides a detailed account of their antibacterial activity, mechanism of action, safety, toxicity, as well as the challenges in terms of solubility/bioavailability and their solutions.
Article
Chemistry, Multidisciplinary
Chen-Xi Yu, Bing-Yan Wei, Xue-Qing Kong, Cai-Guang Yang, Fa-Jun Nan
Summary: The threat posed by MRSA to public health has led to the need for new antibiotics, and the ring-opened bengamide analogue 2j has shown excellent antibacterial activity against MRSA without activating ClpP.
CHINESE JOURNAL OF CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Hae Ju Han, Woong Sub Byun, Gyu Ho Lee, Won Kyung Kim, Kyungkuk Jang, Sehun Yang, Jewon Yang, Min Woo Ha, Suckchang Hong, Jeeyeon Lee, Jongheon Shin, Ki Bong Oh, Sang Kook Lee, Hyeung-geun Park
Summary: DOT1L, a histone H3 methyltransferase, is overexpressed in human breast cancer cells and has been linked to proliferation and metastasis. Non-nucleoside DOT1L inhibitors, such as selenopsammaplin A and its analogues, show promising cytotoxicity and inhibitory activity against DOT1L. Compound 10, a phenyl analogue, exhibits potent antitumor and antimetastatic activity, making it a potential candidate for cancer chemotherapy in breast cancers.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Parteek Prasher, Rabab Fatima, Mousmee Sharma, Bekzat Tynybekov, Asma M. Alshahrani, Dilek Arslan Atessahin, Javad Sharifi-Rad, Daniela Calina
Summary: Lignans, such as honokiol, are plant-derived polyphenolic compounds with small size and hydrophobicity that enable them to interact with proteins in cell membranes. Honokiol, isolated from the genus Magnolia, shows potential as an anticancer agent due to its high bioavailability and ability to regulate signaling pathways associated with oncogenesis, inhibit cell cycle, and prevent metastasis. It also exhibits properties that overcome the bioavailability drawbacks of many contemporary anticancer drugs.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Chemistry, Medicinal
Kristin Beirow, Julia Jedamzik, Lukas Schulig, Konrad W. Wurm, Christian J. Lemmerhirt, Robert K. Hofstetter, Andreas Link, Patrick J. Bednarski
Summary: Flupirtine and retigabine are important drugs for pain and epilepsy, but they have limitations due to hepatotoxicity and tissue discoloration. They are metabolized to reactive metabolites, which cause adverse effects. The metabolic pathway leading to the formation of biologically inactive 4-fluorohippuric acid from flupirtine has been verified through the use of flupirtine analogues. The correlation between in vitro hepatotoxicity and the levels of 4-fluorobenzoic acid may provide valuable information for the design of new flupirtine analogues.
Article
Food Science & Technology
Sandra Raposo-Garcia, M. Carmen Louzao, Haruhiko Fuwa, Makoto Sasaki, Carmen Vale, Luis M. Botana
Summary: Ciguatoxins are causative compounds of ciguatera fish poisoning and their potency is determined as CTX1B > CTX3B > CTX4A > gambierol > gambiemne > MTX3. The activation voltage of sodium channels is more sensitive in detecting ciguatoxins than their effect on peak sodium current amplitude.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Daichi Mizukami, Kei Iio, Mami Oda, Yu Onodera, Haruhiko Fuwa
Summary: Tetrahydropyran-containing macrolactones were synthesized using gold and ruthenium catalysis through a three-step reaction sequence, demonstrating high synthetic efficiency and good diastereoselectivity. The synthesis of an anticancer marine macrolide showcased the potential application of this reaction sequence in the synthesis of natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Maria Carmen Louzao, Natalia Vilarino, Carmen Vale, Celia Costas, Alejandro Cao, Sandra Raposo-Garcia, Mercedes R. Vieytes, Luis M. Botana
Summary: This article discusses the importance of marine phycotoxins and their impact on human health, ecosystems, and the economy. It emphasizes the challenges in setting regulatory limits and conducting monitoring, as well as the demand for universal phycotoxin detectors.
Article
Toxicology
Sandra Raposo-Garcia, Andrea Boente-Juncal, Mercedes Rodriguez-Vieytes, Mercedes Camina, Celia Costas, Alejandro Cao, M. Carmen Louzao, Manuel Cifuentes, Carmen Vale, Luis M. Botana
Summary: Ciguatoxins are marine compounds produced by dinoflagellates that can cause food poisoning. This study investigated the effects of ciguatoxin-related compounds on mice and highlighted the need to reevaluate their in vivo activity. It also emphasized the importance of using standardized procedures and certified reference materials to determine the levels of these environmental contaminants in food.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Food Science & Technology
Celia Costas, M. Carmen Louzao, Sandra Raposo-Garcia, Carmen Vale, Mercedes R. Vieytes, Luis M. Botana
Summary: In this study, the researchers evaluated the effect of Okadaic acid (OA) on diarrhea using mice models. The results showed that OA exposure led to an increase in chloride and sodium concentration in the feces, indicating a secretory diarrhea. However, pre-treatment with cyproheptadine (CPH) attenuated the damage caused by OA in the colon and jejunum. The study identified cellular mechanisms underlying OA-induced diarrhea and highlighted the complex toxicity of this compound.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Chemistry, Medicinal
Celso Alves, Joana Silva, Susete Pinteus, Romina A. Guedes, Rita C. Guedes, Rebeca Alvarino, Rafaela Freitas, Marcia Goettert, Helena Gaspar, Amparo Alfonso, Maria C. Alpoim, Luis M. Botana, Rui Pedrosa
Summary: This study evaluated the cytotoxic and proteasome inhibitory activities of compounds isolated from Sphaerococcus coronopifolius, with potential as anticancer agents. The compounds showed cytotoxic effects on malignant cell lines and induced DNA damage. They also affected mitochondrial function, phosphatidylserine externalization, Caspase-9 activity, and nuclear morphology. Further studies are needed to fully understand the potential of these compounds for anticancer therapeutics.
Article
Chemistry, Multidisciplinary
Kazuk i Nakazato, Mami Oda, Haruhiko Fuwa
Summary: The total synthesis of (+)-neopeltolide, a potent antiproliferative marine macrolide natural product, was achieved in 11 steps from a commercially available inexpensive material. The 14-membered macrolactone skeleton with a 2,6-cis-substituted tetrahydropyran ring was synthesized using a macrocyclization/trans-annular pyran cyclization strategy. The synthesis of the oxazole-containing side chain was achieved through palladium-catalyzed cross-coupling reactions. Additionally, the total synthesis of (+)-9-epi-neopeltolide was accomplished in 12 steps by stereochemical diversification at the C9 position.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2023)
Article
Chemistry, Organic
Ryohei Hanzawa, Haruhiko Fuwa
Summary: A collective asymmetric total synthesis of marine tricyclic alkaloids, cylindricines A-H, as well as the proposed structures of cylindricines I and J, was accomplished from a single common spirocyclic pyrrolidine intermediate in a concise manner. A tandem chemoselective oxidation/intramolecular aza-Michael addition/epimerization strategy was utilized to successfully construct the tricyclic skeleton. This work presents a versatile synthetic approach to the cylindricine family of marine tricyclic alkaloids.
Article
Chemistry, Organic
Yoshihiro Goda, Haruhiko Fuwa
Summary: The total synthesis of (-)-enigmazole B was achieved for the first time using a series of efficient chemical reactions, including olefin cross-metathesis, hemiacetalization/intramolecular oxa-Michael addition sequence, Sonogashira cross-coupling, chemo- and regioselective Au-catalyzed intramolecular alkyne hydroalkoxylation, and Yamaguchi macrolactonization.
Article
Chemistry, Organic
Riko Minami, Tsubasa Kasai, Keisuke Murata, Haruhiko Fuwa
Summary: In this study, a convergent total synthesis of (+)-muricatetrocin B, a tetrahydrofuran-containing acetogenin with potent and selective cytotoxicity against HT-29 human colon adenocarcinoma cell line, was achieved in 13 steps. The synthesis is highlighted by a late-stage sequential olefin cross-metathesis/Hartung-Mukaiyama cyclization for the assembly of the 2,5-trans-substituted tetrahydrofuran ring.
Article
Chemistry, Organic
Haruhiko Fuwa
Summary: In this paper, the development of a new strategy for streamlined synthesis of tetrahydropyran-embedded macrolactones is summarized, as well as its successful implementation in the total synthesis of two natural products. The method enables a reduction in steps and an improvement in synthesis efficiency.
Article
Chemistry, Multidisciplinary
Hayato Nakagawa, Haruhiko Fuwa
Summary: Stereodivergent synthesis of 2,5-disubstituted pyrrolidines was achieved through a Au-catalyzed tandem intramolecular alkyne hydroamination/iminium formation/Et3SiH reduction. The stereochemical outcome could be switched by selecting an appropriate nitrogen protecting group. Total synthesis of a diastereomeric pair of alkaloid natural products, monomorine I and indolizidine 195B, was successfully accomplished to demonstrate the synthetic utility of the tandem reaction.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Sandra Raposo-Garcia, Alejandro Cao, Celia Costas, M. Carmen Louzao, Natalia Vilarino, Carmen Vale, Luis M. Botana
Summary: The expanding microorganisms producing ciguatoxins have raised significant concerns about ciguatera fish poisoning (CF), necessitating the development of a reliable and rapid ciguatoxin detection method to ensure food safety. This study evaluated various cell lines for CTX detection and revealed the limitations of the N2a cell line due to low availability of sodium channels and significant O/V damage. The HEK293 Nav cell line, expressing the alpha 1.6 subunit of sodium channels, proved to be sensitive to ciguatoxin without sensitization with O/V, providing an alternative for sodium channel-targeting compound detection.
