Biological Evaluation of Mitochondria Targeting Small Molecules as Potent Anticancer Drugs

2021 ◽  
pp. 105055
Author(s):  
Shuhua Luo ◽  
Xin Dang ◽  
Juntao Wang ◽  
Chang Yuan ◽  
Yixin Hu ◽  
...  
2016 ◽  
Vol 7 (5) ◽  
pp. 3017-3024 ◽  
Author(s):  
Guocan Yu ◽  
Dan Wu ◽  
Yang Li ◽  
Zhihua Zhang ◽  
Li Shao ◽  
...  

Here we integrate diagnostic and therapeutic agents into a mitochondria-targeting [2]rotaxane, which can be utilized as a drug delivery platform to conjugate anticancer drugs to prepare prodrugs for efficient targeted drug delivery.


2018 ◽  
Vol 14 ◽  
pp. 2646-2650 ◽  
Author(s):  
Abed Tarapdar ◽  
James K S Norris ◽  
Oliver Sampson ◽  
Galina Mukamolova ◽  
James T Hodgkinson

Siderophore–antibiotic conjugates consist of an antibiotic covalently linked by a tether to a siderophore. Such conjugates can demonstrate enhanced uptake and internalisation to the bacterial cell resulting in significantly reduced MIC values and extended spectrum of activity. Phenothiazines are a class of small molecules that have been identified as a potential treatment for multidrug resistant tuberculosis and latent TB. Herein we report the design and synthesis of the first phenothiazine–siderophore conjugate. A convergent synthetic route was developed whereby the functionalised phenothiazine component was prepared in four steps and the siderophore component also prepared in four steps. In M. smegmatis the functionalised phenothiazine demonstrated an equipotent MIC value in direct comparison to the parent phenothiazine from which it was derived. The final conjugate was synthesised by amide bond formation between the two components and global deprotection of the PMB protecting groups to unmask the catechol iron chelating groups of the siderophore. The synthesis is readily amenable to the preparation of analogues whereby the siderophore component of the conjugate can be modified. The route will be used to prepare a library of siderophore–phenothiazine conjugates for full biological evaluation of much needed new antibacterial agents.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Daniela Sorriento ◽  
Antonietta Valeria Pascale ◽  
Rosa Finelli ◽  
Anna Lisa Carillo ◽  
Roberto Annunziata ◽  
...  

Mitochondria are critical regulator of cell metabolism; thus, mitochondrial dysfunction is associated with many metabolic disorders. Defects in oxidative phosphorylation, ROS production, or mtDNA mutations are the main causes of mitochondrial dysfunction in many pathological conditions such as IR/diabetes, metabolic syndrome, cardiovascular diseases, and cancer. Thus, targeting mitochondria has been proposed as therapeutic approach for these conditions, leading to the development of small molecules to be tested in the clinical scenario. Here we discuss therapeutic interventions to treat mitochondrial dysfunction associated with two major metabolic disorders, metabolic syndrome, and cancer. Finally, novel mechanisms of regulation of mitochondrial function are discussed, which open new scenarios for mitochondria targeting.


NANO ◽  
2008 ◽  
Vol 03 (04) ◽  
pp. 229-232 ◽  
Author(s):  
A. ERDEM ◽  
H. KARADENIZ ◽  
A. CALISKAN ◽  
A. VASEASHTA

The objective of this investigation is to understand the nature and dynamics of binding small molecules to bio-macromolecules using electrochemical methods. The investigation pertaining to the design of site- and conformation-specific reagents provides a rationale for new studies of drug delivery design. Some anticancer drugs and DNA interactions have been undertaken by using a variety of techniques. Determination of interaction between DNA and DNA-targeted molecules would be valuable in the design of molecule-specific electrochemical biosensors for applications in diagnostics, development of drugs for chemotherapy, and as a biotechnological tool for DNA-based point-of-care diagnosis.


2013 ◽  
Vol 19 (52) ◽  
pp. 17871-17880 ◽  
Author(s):  
Luciano Oehninger ◽  
Laura Nadine Küster ◽  
Claudia Schmidt ◽  
Alvaro Muñoz-Castro ◽  
Aram Prokop ◽  
...  

Life Sciences ◽  
1989 ◽  
Vol 45 (26) ◽  
pp. 2569-2575 ◽  
Author(s):  
Yao-zu Chen ◽  
Yang-guang Wang ◽  
Jim-xin Li ◽  
Xuan Tian ◽  
Zhen-pin Jia ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Long Tang ◽  
Jianchun Jiang ◽  
Guoqiang Song ◽  
Yajing Wang ◽  
Ziheng Zhuang ◽  
...  

AbstractA series of urolithins derivatives were designed and synthesized, and their structures have been confirmed by 1H NMR, 13C NMR, and HR-MS. The inhibitory activity of these derivatives on phosphodiesterase II (PDE2) was thoroughly studied with 3-hydroxy-8-methyl-6H-benzo[C]chromen-6-one and 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[C] chromen-6-one as the lead compounds. The biological activity test showed that compound 2e had the best inhibitory activity on PDE2 with an IC50 of 33.95 μM. This study provides a foundation for further structural modification and transformation of urolithins to obtain PDE2 inhibitor small molecules with better inhibitory activity.


MedChemComm ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 27-43 ◽  
Author(s):  
Shiva Krishna Reddy Guduru ◽  
Prabhat Arya

This review describes mammalian target of rapamycin (mTOR) structure with key role in biological system and selected case studies related to the synthesis of rapamycin-derived and hybrid molecules to explore their biological properties.


2010 ◽  
Vol 6 (1) ◽  
pp. 6-8 ◽  
Author(s):  
Xing Zheng ◽  
Fei Fei Zhao ◽  
Yun Mei Liu ◽  
Xu Yao ◽  
Zi Tong Zheng ◽  
...  

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