Article
Chemistry, Medicinal
Jinsheng Cui, Suhyun Ye, Daniel Shin, Illhwan Cho, Hye Yun Kim, Yun Kwon, Keunwan Park, Sang-Jip Nam, YoungSoo Kim, Dong-Chan Oh
Summary: Two new glycosylated and succinylated macrocyclic lactones, succinyl glyco-oxydifficidin (1) and succinyl macrolactin O (2), were isolated from a Bacillus strain collected from an intertidal mudflat on Anmyeon Island in Korea. Their planar structures were proposed using mass spectrometric analysis and NMR spectroscopic data, while the absolute configurations were determined through various methods. Biological evaluation showed that both compounds have potential therapeutic effects in inhibiting and dissociating amyloid beta (A beta) aggregation.
Article
Microbiology
Kaetlyn T. Ryan, Nicolas J. Wheeler, Isaac K. Kamara, Hailey Johnson, Judith E. Humphries, Mostafa Zamanian, John D. Chan
Summary: Macrocyclic lactones are commonly used to treat parasitic roundworm infections, but their activity against parasitic flatworms has not been thoroughly studied. Ivermectin, a prototypical macrocyclic lactone, is known to be ineffective against flatworms. However, other macrocyclic lactones may have antiparasitic activity on flatworms. In this study, an automated imaging assay combined with measurement of lactate levels was used to screen 21 macrocyclic lactones against adult schistosomes. Several macrocyclic lactones were identified to cause paralysis and lack of lactate production in vitro, but further testing in mice did not show a reduction in worm burden.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Plant Sciences
L. Laber, C. Eichberg, A. Zimmerbeutel, R. A. Duering, T. W. Donath
Summary: Macrocyclic lactone anthelmintics have significant effects on seed germination, altering germination percentage and mean germination time, with specific effects varying between species and pharmaceuticals.
Article
Biochemistry & Molecular Biology
Adam McDermott-Rouse, Eleni Minga, Ida Barlow, Luigi Feriani, Philippa H. Harlow, Anthony J. Flemming, Andre E. X. Brown
Summary: High-throughput imaging and quantitative phenotyping can be used to measure Caenorhabditis elegans behavioral responses to compounds and predict their mode of action accurately. This method could accelerate the discovery of mode of action in invertebrate-targeting compound development and refine mode of action categories.
MOLECULAR SYSTEMS BIOLOGY
(2021)
Article
Chemistry, Medicinal
Hakmin Mun, Helen Elizabeth Townley
Summary: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in pediatric patients, with low survival rates for relapsed or refractory cases. This study found that helenalin promotes RMS cell death in vitro through mechanisms such as increasing oxidative stress levels and decreasing mitochondrial membrane potential.
Article
Biochemistry & Molecular Biology
Wei Luo, Kaiyue Wang, Jingyi Luo, Yingchen Liu, Jiawen Tong, Mengting Qi, Yue Jiang, Yong Wang, Zhiqing Ma, Juntao Feng, Bin Lei, He Yan
Summary: The main component of orange peel essential oil, limonene, has antibacterial, antiseptic, and antitumor activity, and is of great value in agriculture. It has been found that limonene exhibits excellent antiviral activity against tobacco mosaic virus (TMV), and it triggers a hypersensitive response in tobacco. Limonene also enhances defense enzyme activity and the expression of defense-related genes, as well as the accumulation of salicylic acid. Furthermore, it has been shown to induce plant resistance against various pathogens in pot experiments.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2023)
Review
Parasitology
Roger K. Prichard
Summary: Heartworm disease, caused by Dirofilaria immitis and transmitted by mosquitoes, is a lethal disease in dogs and cats. Prevention primarily relies on macrocyclic lactones, with resistance to these drugs being an important issue that requires better testing methods for confirmation and surveillance of resistance levels. Additional research and development of new classes of heartworm preventives are needed to combat the spread of resistance and further disease.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ruyu Wang, Guanglei Zhai, Guanghao Zhu, Mengge Wang, Xiaoyi Gong, Weidong Zhang, Guangbo Ge, Hongzhuan Chen, Lili Chen
Summary: This study identified Thonzonium bromide as an effective inhibitor of SARS-CoV-2 3CLpro, the viral proteinase responsible for replication and transcription of the virus. Thonzonium bromide showed better inhibitory activity than other analogues and demonstrated a broad-spectrum inhibitory activity against human coronaviruses. It functions by occupying the catalytic site and inducing conformational changes of the protease.
BIOORGANIC CHEMISTRY
(2023)
Article
Toxicology
Michaela Sadibolova, Risto O. Juvonen, Seppo Auriola, Iva Bousova
Summary: This study investigates the metabolism of helenalin, a sesquiterpene lactone used in European and Chinese folk medicine, revealing differences in metabolic pathways between rats and humans. In humans, hepatic enzymes CYP2B6, CYP3A4, CYP3A5, and CYP3A7, as well as extrahepatic CYP2A13, play significant roles in metabolizing helenalin. The study also shows that helenalin acts as an inhibitor of CYP3A4, CYP3A5, and a mechanism-based inhibitor of CYP2A13.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
An-Ping Li, Ying-Hui He, Shao-Yong Zhang, Yan-Ping Shi
Summary: Phytopathogenic bacteria, the most difficult plant disease to control, cause significant losses to agricultural products and the economy globally. This study evaluated 50 flavonoids for their antibacterial activities against two challenging plant bacterial pathogens and found that kaempferol exhibited excellent antibacterial activity against Xanthomonas oryzae (Xo) and quercetin showed the best antibacterial activity against Xanthomonas axo-nopodis pv citri (Xac). Further investigation revealed that kaempferol mainly exerted bacteriostatic effects by affecting bacterial energy metabolism, reducing pathogenicity, and leading to cellular damage and death.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2022)
Review
Parasitology
Molly D. Savadelis, Tom L. McTier, Kristina Kryda, Steven J. Maeder, Debra J. Woods
Summary: Heartworm disease remains a significant and pathogenic disease in dogs, despite the regular use of preventive products. Some strains of D. immitis have developed resistance to the only available drug class, macrocyclic lactones (MLs), for heartworm prevention in the United States. The optimization of dose and formulation of moxidectin provides a unique opportunity to improve efficacy against ML-resistant strains. Two new products, ProHeart (R) 12 and Simparica Trio (R), have demonstrated 100% preventive efficacy against recent field strains of heartworm, offering important advances in heartworm prevention for veterinarians and pet owners.
PARASITES & VECTORS
(2022)
Article
Chemistry, Medicinal
Candice Soares de Melo, Vinayak Singh, Alissa Myrick, Sandile B. Simelane, Dale Taylor, Christel Brunschwig, Nina Lawrence, Dirk Schnappinger, Curtis A. Engelhart, Anuradha Kumar, Tanya Parish, Qin Su, Timothy G. Myers, Helena I. M. Boshoff, Clifton E. Barry, Frederick A. Sirgel, Paul D. van Helden, Kirsteen Buchanan, Tracy Bayliss, Simon R. Green, Peter C. Ray, Paul G. Wyatt, Gregory S. Basarab, Charles J. Eyermann, Kelly Chibale, Sandeep R. Ghorpade
Summary: Phenotypic screening of a compound library against Mycobacterium tuberculosis led to the identification of a cluster of pan-active compounds with a novel mechanism of action. These compounds exerted bactericidal effects on replicating Mtb and showed potential resistance mechanisms involving mutations in MmpL3.RNA transcriptional profiling and checkerboard 2D-MIC assays suggested perturbation of Fe-homeostasis by the compounds. Structure-activity relationship studies identified potent compounds with good physicochemical properties and moderate selectivity over cytotoxicity against mammalian cell lines.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Medicine, General & Internal
Qi-Yu Zhang, Zhi-Bin Yan, Yue-Ming Meng, Xiang-Yu Hong, Gang Shao, Jun-Jie Ma, Xu-Rui Cheng, Jun Liu, Jian Kang, Cai-Yun Fu
Summary: Antimicrobial peptides (AMPs) are a promising candidate to combat antibiotic resistant bacteria, showing broad-spectrum antimicrobial activity with low toxicity and utilizing sophisticated mechanisms of action. This comprehensive review provides an overview of the origin, structural characteristics, mechanisms of action, biological activities, and clinical applications of AMPs. Strategies to optimize and develop AMP-based treatments for potential antimicrobial and anticancer therapeutics are also discussed.
MILITARY MEDICAL RESEARCH
(2021)
Article
Plant Sciences
Abosede N. Ogedengbe-Olowofoyeku, Isaiah O. Ademola, Colin W. Wright, Sunday O. Idowu, Amos A. Fatokun
Summary: The study aimed to isolate and characterize anthelmintic compounds from S. mombin leaves, demonstrating the anthelmintic activity of phaeophorbide-a and its lack of toxicity to mammalian cells. It represents a potential lead for novel anthelmintic development.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Review
Medicine, Research & Experimental
Ghader Babaei, Shiva Gholizadeh-Ghaleh Aziz, Masoumeh Rajabi Bazl, Mohammad Hassan Khadem Ansari
Summary: Cancer is a major challenge for human societies, with natural products like Alantolactone (ALT) being studied for their anti-cancer properties by inhibiting signaling pathways and generating free radicals. These studies aim to introduce the latest molecular mechanisms of ALT proposed by researchers in recent years.
BIOMEDICINE & PHARMACOTHERAPY
(2021)