Design and synthesis of novel aza-ursolic acid derivatives: in vitro cytotoxicity and nitric oxide release inhibitory activity. 2022

Mingzhu Luan, and Yaoyao Xu, and Xiaofan Zhang, and Dalei Li, and Mengjun Yan, and Guige Hou, and Qingguo Meng, and Feng Zhao, and Fenglan Zhao
School of Pharmacy, Key Laboratory of Molecular Pharmacology & Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System & Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, PR China.

Aim: Inducible nitric oxide synthase (iNOS) is a validated target for anti-inflammatory treatment. Based on the authors' previous work, novel aza-ursolic acid derivatives were designed and synthesized and their inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) release from RAW264.7 cells was evaluated. Materials & results: 16 novel derivatives were screened for their in vitro inhibitory activity against NO release using Griess assays and the cytotoxicity was evaluated using MTT assays. The presence of furoxan joined to the A-ring of ursolic acid and N-methylpiperazine groups in the lead compound was identified for anti-inflammatory activity, and compound 21b showed 94.96% inhibition of NO release at 100 μM with an IC50 value of 8.58 μM. Conclusion: Compound 21b has potential anti-inflammatory activity with low cytotoxicity that warrants further preclinical study and evaluation.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D000067996 RAW 264.7 Cells A transformed macrophage cell line isolated from ASCITES of mice infected with ABELSON MURINE LEUKEMIA VIRUS. RAW 264.7 Cell Line,264.7 Cell, RAW,264.7 Cells, RAW,Cell, RAW 264.7,Cells, RAW 264.7,RAW 264.7 Cell
D000097245 Ursolic Acid A pentacyclic triterpene that co-occurs with its isomer OLEANOLIC ACID in several plant species, and occurs in large amounts in FRUITS (such as CRANBERRIES; PEARS; PLUMS; and OLIVES), MEDICINAL HERBS, and other plants. (+)-Ursolic Acid,(3 beta)-3-Hydroxyurs-12-en-28-oic Acid,3-Epi-Ursolic Acid,3-Epiursolic Acid,3alpha-Ursolic Acid,3beta-Ursolic Acid,Olean-12-en-28-oic Acid, 3-Hydroxy-, Sodium Salt (1:1), (3beta)-,Sodium Oleanolate,Ursolic Acid Monosodium Salt,Ursolic Acid Sodium Salt,Ursolic Acid, (3beta)-Isomer, 2-(14)C-Labeled,Ursolic Acid, (3beta)-Isomer, Monopotassium Salt,Merotaine,3 Epi Ursolic Acid,3 Epiursolic Acid,3alpha Ursolic Acid,3beta Ursolic Acid,Oleanolate, Sodium
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014315 Triterpenes A class of terpenes (the general formula C30H48) formed by the condensation of six isoprene units, equivalent to three terpene units. Triterpene,Triterpenoid,Triterpenoids
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D052247 Nitric Oxide Synthase Type II A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES. INOS Enzyme,Inducible NOS Protein,Inducible Nitric Oxide Synthase,NOS-II,Nitric Oxide Synthase II,Nitric Oxide Synthase, Type II,NOS II

Related Publications

Mingzhu Luan, and Yaoyao Xu, and Xiaofan Zhang, and Dalei Li, and Mengjun Yan, and Guige Hou, and Qingguo Meng, and Feng Zhao, and Fenglan Zhao
June 2010, Molecules (Basel, Switzerland),
Mingzhu Luan, and Yaoyao Xu, and Xiaofan Zhang, and Dalei Li, and Mengjun Yan, and Guige Hou, and Qingguo Meng, and Feng Zhao, and Fenglan Zhao
September 2017, Bioorganic & medicinal chemistry letters,
Mingzhu Luan, and Yaoyao Xu, and Xiaofan Zhang, and Dalei Li, and Mengjun Yan, and Guige Hou, and Qingguo Meng, and Feng Zhao, and Fenglan Zhao
May 2015, European journal of medicinal chemistry,
Mingzhu Luan, and Yaoyao Xu, and Xiaofan Zhang, and Dalei Li, and Mengjun Yan, and Guige Hou, and Qingguo Meng, and Feng Zhao, and Fenglan Zhao
January 2016, Journal of Asian natural products research,
Mingzhu Luan, and Yaoyao Xu, and Xiaofan Zhang, and Dalei Li, and Mengjun Yan, and Guige Hou, and Qingguo Meng, and Feng Zhao, and Fenglan Zhao
August 2015, European journal of medicinal chemistry,
Mingzhu Luan, and Yaoyao Xu, and Xiaofan Zhang, and Dalei Li, and Mengjun Yan, and Guige Hou, and Qingguo Meng, and Feng Zhao, and Fenglan Zhao
December 2012, European journal of medicinal chemistry,
Mingzhu Luan, and Yaoyao Xu, and Xiaofan Zhang, and Dalei Li, and Mengjun Yan, and Guige Hou, and Qingguo Meng, and Feng Zhao, and Fenglan Zhao
December 2022, European journal of medicinal chemistry,
Mingzhu Luan, and Yaoyao Xu, and Xiaofan Zhang, and Dalei Li, and Mengjun Yan, and Guige Hou, and Qingguo Meng, and Feng Zhao, and Fenglan Zhao
February 2009, Archiv der Pharmazie,
Mingzhu Luan, and Yaoyao Xu, and Xiaofan Zhang, and Dalei Li, and Mengjun Yan, and Guige Hou, and Qingguo Meng, and Feng Zhao, and Fenglan Zhao
September 2014, Journal of medicinal chemistry,
Mingzhu Luan, and Yaoyao Xu, and Xiaofan Zhang, and Dalei Li, and Mengjun Yan, and Guige Hou, and Qingguo Meng, and Feng Zhao, and Fenglan Zhao
August 2008, Journal of medicinal chemistry,
Copied contents to your clipboard!