Article
Chemistry, Organic
Krishnaiah Kumari, Tasqeeruddin Syed, A. M. S. Krishna, Subhashini Muvvala, Annpurna Nowduri, Chidara Sridhar, Abhishek Saxena
Summary: A novel synthetic route for the total synthesis of neocosmosin B from inexpensive and commercially available starting materials was described. This synthesis strategy, which utilizes alkylation of 1,3-dithiane, Sharpless dihydroxylation, and Yamaguchi macro-lactonization as key steps, could also be useful for the synthesis of other related resorcylic acid lactones.
Article
Biochemistry & Molecular Biology
Ying Gao, Jia Zhou, Xianggao Meng, Qianxi Ouyang, Yutian Gan, Hanli Ruan
Summary: Eleven previously undescribed radicicol-type resorcylic acid lactones were isolated and identified from a soil-derived fungus. Some of these compounds displayed immunosuppressive activities against T and B cell proliferation, suggesting the importance of the α,β-unsaturated ketone from C-8 to C-10. Further study revealed that one compound exerted anti-proliferative effect on T lymphocytes through Hsp90 inhibition.
BIOORGANIC CHEMISTRY
(2022)
Article
Plant Sciences
Zeinab Y. Al Subeh, Tian Li, Abraham Ustoyev, Jennifer C. Obike, Philip M. West, Manead Khin, Joanna E. Burdette, Cedric J. Pearce, Nicholas H. Oberlies, Mitchell P. Croatt
Summary: In this study, a step-economical approach was used to synthesize 35 C8-C9 diol analogues through nonselective reactions, showing their potential as anti-tumor agents with TAK1 inhibitory activity and cytotoxicity against ovarian and breast cancer cell lines.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Biochemistry & Molecular Biology
Ying Gao, Fangfang Duan, Jinling Chang, Xianggao Meng, Hanli Ruan
Summary: In this study, Podomycins A-L (1-12) were characterized from an endophyte harbored in the roots of Sanguisorba officinalis L. The structures of these compounds were determined through various methods, and their biological activities were evaluated. Compound 6, in particular, showed immunosuppressive activity by inducing apoptosis in activated T cells via the MAPKs/AKT pathway.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Sunghee Bang, Jaekyeong Kim, Jiwon Oh, Ji-Seok Kim, Seong-Ryong Yu, Stephen Deyrup, Yong-Sun Bahn, Sang Hee Shim
Summary: Six new beta-resorcylic acid derivatives were isolated from a fungus associated with a halophyte, along with four previously reported derivatives. The stereochemistry of one of the compounds was determined. The structures of the isolated compounds were elucidated using spectroscopic and chemical analysis. Two of the compounds showed potent antifungal activity against Cryptococcus neoformans.
Article
Chemistry, Multidisciplinary
Siwen Niu, Dong Liu, Zongze Shao, Jiang Huang, Aili Fan, Wenhan Lin
Summary: The study isolated eight compounds from a deep-sea-derived Spiromastix fungus, with compound 3 showing potent activities against Gram-positive pathogenic bacteria. The chemical diversity of chlorinated natural products from marine-derived fungi is extended by this research, providing a promising lead for the development of antibacterial agents.
Article
Plant Sciences
Laura Flores-Bocanegra, Zeinab Y. Al Subeh, Joseph M. Egan, Tamam El-Elimat, Huzefa A. Raja, Joanna E. Burdette, Cedric J. Pearce, Roger G. Linington, Nicholas H. Oberlies
Summary: This study evaluated the performance of MADByTE for compound dereplication and found that MADByTE is effective for detecting specific compound classes in complex mixtures and can successfully predict compound members in the sample set.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Biochemistry & Molecular Biology
Mayu Yoshida, Haruna Nagao, Hajime Sugiyama, Masaaki Sawa, Takayoshi Kinoshita
Summary: In this study, a novel ERK2 inhibitor was discovered through in silico screening, which binds to a new binding site instead of the traditional allosteric site. This finding suggests the feasibility of developing new types of ERK2 inhibitors.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Plant Sciences
Jacob P. Walsh, David R. McMullin, Ken K-C Yeung, Mark W. Sumarah
Summary: Ilyonectria mors-panacis, formerly known as Cylindrocarpon destructans, is the main plant pathogen causing ginseng root rot, which significantly reduces crop yields. This study focused on the secondary metabolites produced by I. mors-panacis and their roles in the disease process. Results showed that pathogenic strains produce resorcylic acid lactones, while avirulent strains do not, indicating a potential link between these metabolites and disease severity.
PHYTOCHEMISTRY LETTERS
(2022)
Article
Plant Sciences
Hong Chuan Song, Dan Qin, Hai Yang Liu, Jin Yan Dong, Chuan You, Yu Meng Wang
Summary: In this study, several new and known compounds were isolated from the endophytic fungus Penicillium ochrochloron SWUKD4.1850 from the medicinal plant Kadsura angustifolia. Penochrochlactone C demonstrated moderate cytotoxicity against HeLa tumor cells, while compounds 4-6 exhibited moderate antibacterial activities against various bacteria.
Article
Chemistry, Multidisciplinary
Yancong Tian, Martin Jakoobi, Roman Boulatov, Alexey G. Sergeev
Summary: This study reveals a unique mechanism of transition metal insertion into aromatic rings, requiring cooperativity of two iridium centers. The research provides insight into the role of metal-metal cooperativity in the cleavage of C-C bonds.
Article
Chemistry, Applied
Kalidasu Sheelam, Sridhar Chidara, Srilalitha Vinnakota, Gattu Sridhar, Ravikumar Polothi
Summary: An efficient and stereoselective total synthesis of (3R, 4S)-4-hydroxylasiodiplodin has been achieved starting from known starting materials. The key steps involved in this synthesis are Stille cross coupling, alkylation of 1,3-dithiane, and Yamaguchi macrolactonization.
NATURAL PRODUCT RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Shilpa Kuttikrishnan, Kirti S. Prabhu, Ahmed H. Al Sharie, Yazan O. Al Zu'bi, Feras Q. Alali, Nicholas H. Oberlies, Aamir Ahmad, Tamam El-Elimat, Shahab Uddin
Summary: This review focuses on the structures, isolation, occurrence, biological activities, and anticancer molecular mechanisms of natural RALs with cytotoxic activities.
DRUG DISCOVERY TODAY
(2022)
Article
Chemistry, Multidisciplinary
Ben A. Russell, Mario Gonzalez-Jimenez, Nikita V. Tukachev, Laure-Anne Hayes, Tajrian Chowdhury, Uros Javornik, Gregor Mali, Manlio Tassieri, Joy H. Farnaby, Hans M. Senn, Klaas Wynne
Summary: This study discovered a single-component homogeneous molecular liquid that exhibits two comparable glass transitions, one associated with dynamic arrest of liquid properties and the other associated with the freezing out of intramolecular degrees of freedom.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Plant Sciences
Xiang Guo, Qinyu Meng, Siwen Niu, Jie Liu, Xingchen Guo, Zhaolun Sun, Dong Liu, Yucheng Gu, Jian Huang, Aili Fan, Wenhan Lin
Summary: Epigenetic manipulation of a deep-sea sediment-derived Spiromastix sp. fungus resulted in the isolation of nine new guaiane-type sesquiterpenes, with compound 5 demonstrating significant anti-neuroinflammatory activity by inhibiting NF-kappa B translocation and reducing pro-inflammatory cytokine levels in microglial cells. This study provides valuable insights into the cellular-level activity of guaiane-type sesquiterpenoids and suggests compound 5 as a promising candidate for further optimization as a multifunctional agent for anti-neuroinflammation.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Biochemistry & Molecular Biology
Pasquale Linciano, Rosaria Benedetti, Luca Pinzi, Fabiana Russo, Ugo Chianese, Claudia Sorbi, Lucia Altucci, Giulio Rastelli, Livio Brasili, Silvia Franchini
Summary: HDAC inhibitors play a significant role in cancer treatment, but their lack of selectivity is a major drawback. Researchers have explored novel linker chemotypes to achieve selective inhibition of different HDAC isoforms. Through in vitro tests and docking calculations, it was found that some candidates could selectively inhibit HDAC1 or HDAC6.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Annachiara Tinivella, Luca Pinzi, Giulio Rastelli
Summary: The development of selective inhibitors for human Carbonic Anhydrase isoforms IX and XII is essential for cancer drug research. Machine learning classification models trained on high confidence data from ChEMBL were used to predict ligand activity and selectivity profiles. The results outperformed classic models built with a priori activity thresholds.
JOURNAL OF CHEMINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Virginia Brighenti, Ramona Iseppi, Luca Pinzi, Annamaria Mincuzzi, Antonio Ippolito, Patrizia Messi, Simona Marianna Sanzani, Giulio Rastelli, Federica Pellati
Summary: The study investigated the inhibition ability of pomegranate phenolic compounds on plant and human fungal pathogens, identifying topoisomerases I and II as potential biological targets of punicalagin. Results suggest that punicalagin is a valuable candidate for combating human fungal infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Davide Bonanni, Andrea Citarella, Davide Moi, Luca Pinzi, Elisa Bergamini, Giulio Rastelli
Summary: The design of multi-target drugs is a growing field in medicinal chemistry, especially for complex diseases like cancer. This review focuses on the interplay between HDAC6 and Hsp90, two important targets for multi-target drug design. Crystallographic structures of HDAC6 and Hsp90 complexes are extensively reviewed, providing useful guidelines for the design of dual inhibitors.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Luca Pinzi, Annachiara Tinivella, Giulio Rastelli
Summary: The Tau protein is important in neuronal cells, but its abnormal aggregation can lead to Tauopathies. Current treatments to reduce Tau aggregation are lacking, and there is a need for effective compounds with specific structural guidance.
Article
Biochemistry & Molecular Biology
Luca Pinzi, Annachiara Tinivella, Luca Gagliardelli, Domenico Beneventano, Giulio Rastelli
Summary: Despite available in silico drug design tools, results are often challenging to integrate or utilize fully; Multi-target ligand rational design and drug repurposing are gaining attention; Computational tools and data-driven approaches can reveal new drug discovery opportunities, and LigAdvisor integrates various database information to facilitate drug discovery tasks.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Medicinal
Luca G. Iacovino, Luca Pinzi, Giorgio Facchetti, Beatrice Bortolini, Michael S. Christodoulou, Claudia Binda, Giulio Rastelli, Isabella Rimoldi, Daniele Passarella, Maria Luisa Di Paolo, Lisa Dalla Via
Summary: A library of monosubstituted chalcones with electron-donating and electron-withdrawing groups on aromatic rings was selected for evaluation. Compounds 13 and 14 were found to inhibit MAO-B and may be worth considering as novel MAO-B-selective inhibitors for neurodegenerative disease treatment.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Review
Chemistry, Multidisciplinary
Andrea Citarella, Davide Moi, Luca Pinzi, Davide Bonanni, Giulio Rastelli
Summary: The hydroxamic acid (HA) moiety has gained notoriety in synthetic medicinal chemistry since the approval of three HDAC inhibitors as anticancer drugs. HAs are known for their ability to chelate metal ions, particularly Fe(III) and Zn(II), making them attractive metal binding groups with wide applications as metalloenzymes inhibitors. This review discusses the physicochemical characteristics of HAs, methods for their introduction into organic substrates, and their uses in medicinal chemistry.
Article
Chemistry, Medicinal
Annachiara Tinivella, Jerome C. Nwachukwu, Andrea Angeli, Francesca Foschi, Anna Laura Benatti, Luca Pinzi, Tina Izard, Marta Ferraroni, Rangarajan Erumbi, Michael S. Christodoulou, Daniele Passarella, Claudiu T. Supuran, Kendall W. Nettles, Giulio Rastelli
Summary: In this study, a ligand-based and structure-based multi-target repurposing strategy was used to investigate hexahydrocyclopenta[c]quinoline compounds. Human Carbonic Anhydrases (hCA) and Estrogen Receptors (ER) were identified as top candidates for dual modulation. Two new compounds were designed and synthesized, which directly modulate the activities of both hCA and ER. These compounds showed potent inhibition of cancer cell proliferation and selectivity for different cell types. This study lays the foundation for optimizing the multi-target activity of hCA and ER.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Francesca Foschi, Annachiara Tinivella, Valentina Crippa, Luca Pinzi, Luca Mologni, Daniele Passarella, Giulio Rastelli
Summary: This study reported the design and synthesis of novel anticancer drugs targeting EGFR protein kinase. By studying analogues of a previously identified hit compound, two compounds with improved activity against double mutant EGFR and interesting anti-proliferative activity against NSCLC cancer cells were discovered. These newly discovered compounds represent promising starting points for further optimization.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Davide Bonanni, Luca Pinzi, Giulio Rastelli
Summary: Prostate cancer is the most common type of cancer in men and effective therapeutic answers are urgently needed. By developing machine learning models, researchers were able to predict the activity of potential therapeutics for prostate cancer, achieving prediction performances with MCC values above 0.60 for PC-3 and DU-145 cells.
JOURNAL OF CHEMINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Leonardo Bernal, Luca Pinzi, Giulio Rastelli
Summary: Prostate cancer (PC) is a common cancer in males with poor prognosis in advanced stages. Current therapeutic options are limited and not very effective. This study analyzed compounds with anti-proliferative activity on PC cell lines and identified potential drugs for repurposing against PC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Luca Pinzi, Nicolo Bisi, Claudia Sorbi, Silvia Franchini, Nicolo Tonali, Giulio Rastelli
Summary: Tau is a protein with large structural portions that undergo extended conformational changes. Accumulation of Tau protein into toxic aggregates in neuronal cells leads to severe tauopathies. Recent research advancements have provided a better understanding of Tau structures and their implications in different tauopathies. This review presents an up-to-date overview of Tau structures reported in the Protein Data Bank, focusing on the connections between structural features, tauopathies, crystallization conditions, and sample types. The information presented highlights interesting links that could aid in the design of compounds to modulate Tau aggregation.
Article
Chemistry, Multidisciplinary
Davide Moi, Andrea Citarella, Davide Bonanni, Luca Pinzi, Daniele Passarella, Alessandra Silvani, Clelia Giannini, Giulio Rastelli
Summary: In this study, two potent and selective HDAC6 inhibitors were obtained through chemoinformatic analysis. The newly discovered aminotriazole-based compounds showed higher inhibitory activity and have the potential to be optimized as anticancer compounds.
Article
Biochemistry & Molecular Biology
Pasquale Linciano, Luca Pinzi, Silvia Belluti, Ugo Chianese, Rosaria Benedetti, Davide Moi, Lucia Altucci, Silvia Franchini, Carol Imbriano, Claudia Sorbi, Giulio Rastelli
Summary: Histone deacetylase 6 (HDAC6) inhibitors based on a novel 3-hydroxy-isoxazole ZBG were synthesized and tested for their efficacy. Some compounds showed potent inhibition of HDAC6 with the best candidate reaching an IC50 of 700 nM, making them attractive for further studies. Additionally, the most active inhibitors were investigated for their effects on histone H3 and alpha-tubulin acetylation levels, as well as anti-proliferative activity in DU145 cells.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
