The 4-aminoquinoline drugs, such as chloroquine (CQ), amodiaquine or piperaquine, are still commonly used for malaria treatment, either alone (CQ) or in combination with artemisinin derivatives. We previously described the excellent in vitro activity of a novel pyrrolizidinylmethyl derivative of 4-amino-7-chloroquinoline, named against drug-resistant parasites. Here, we report the optimized and safer synthesis of , now suitable for a scale-up, and its additional in vitro and in vivo characterization. is active against a panel of and field isolates, either alone or in combination with artemisinin derivatives. In vivo is orally active in the and models of rodent malaria with efficacy comparable, or better, than that of CQ and of other quinolines under development. The in vivo and in vitro ADME-Tox studies indicate that possesses a very good pre-clinical developability profile associated with an excellent oral bioavailability, and low toxicity in non-formal preclinical studies on rats, dogs, and non-human primates (NHP). In conclusion, the pharmacological profile of is in line with those obtained with CQ or the other quinolines in use and seems to possess all the requirements for a developmental candidate.
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http://dx.doi.org/10.3390/biom13050836 | DOI Listing |
Appl Biochem Biotechnol
January 2025
Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, 575018, Karnataka, India.
Gymnostachyum febrifugum, a less-known ethnomedicinal plant from the Western Ghats of India, is used to treat various diseases and serves as an antioxidant and antibacterial herb. The present study aims to profile the cytotoxic phytochemicals in G. febrifugum roots using GC-MS/MS, in vitro confirmation of cytotoxic potential against breast cancer and an in silico study to understand the mechanism of action.
View Article and Find Full Text PDFAnn Med
December 2025
Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China.
Background: Non-small cell lung cancer (NSCLC) is a fatal disease, and radioresistance is an important factor leading to treatment failure and disease progression. The objective of this research was to detect radioresistance-related genes (RRRGs) with prognostic value in NSCLC.
Methods: The weighted gene coexpression network analysis (WGCNA) and differentially expressed genes (DEGs) analysis were performed to identify RRRGs using expression profiles from TCGA and GEO databases.
Nutrients
December 2024
Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, University of Florence, 50139 Florence, Italy.
Background: Oxaliplatin-induced neuropathy (OIN) is a severe painful condition that strongly affects the patient's quality of life and cannot be counteracted by the available drugs or adjuvants. Thus, several efforts are devoted to discovering substances that can revert or reduce OIN, including natural compounds. The carob tree, L.
View Article and Find Full Text PDFNutrients
December 2024
Institute of Quality Standards and Testing Technology for Agro-Products of Chinese Academy of Agricultural Sciences, Beijing 100081, China.
Background/objectives: Polyphenols represent a new strategy of dietary intervention for heat stress regulation.
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Results: Lipid metabolism, energy metabolism, and nervous system pathways were the key metabolic regulatory pathways.
Nutrients
December 2024
Pharmacology Laboratory, Department of Medicine, University of Patras, 26500 Rio Achaia, Greece.
Background/objectives: Lavender has been utilized for its medicinal properties since ancient times, with numerous health benefits reported. This study aimed to valorize solid waste from lavender essential oil production by developing a novel lavender extract from solid lavender residues. The extract's preclinical safety and efficacy were evaluated with emphasis on plasma lipid and lipoprotein metabolism, glucose tolerance, and adipose tissue metabolic activity.
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