34000-28-7Relevant articles and documents
Phototransformation of 3-alkoxychromenones: Regioselective photocyclisation and dealkoxylation
Khanna, Radhika,Dalal, Aarti,Kumar, Ramesh,Kamboj, Ramesh C.
, p. 2195 - 2202 (2015)
The phototransformation of some 2-(3-methoxyphenyl)-4H-chromen-4-ones bearing a propynyloxy moiety at the 3-position has been described. On photolysis with pyrex-filtered UV light from a Hg lamp (125 W), these chromenones produced a major amount of 5-ethy
Synthesis, inverse docking-assisted identification and in vitro biological characterization of Flavonol-based analogs of fisetin as c-Kit, CDK2 and mTOR inhibitors against melanoma and non-melanoma skin cancers
Roy, Tithi,Boateng, Samuel T.,Banang-Mbeumi, Sergette,Singh, Pankaj K.,Basnet, Pratik,Chamcheu, Roxane-Cherille N.,Ladu, Federico,Chauvin, Isabel,Spiegelman, Vladimir S.,Hill, Ronald A.,Kousoulas, Konstantin G.,Nagalo, Bolni Marius,Walker, Anthony L.,Fotie, Jean,Murru, Siva,Sechi, Mario,Chamcheu, Jean Christopher
, (2021/01/14)
Due to hurdles, including resistance, adverse effects, and poor bioavailability, among others linked with existing therapies, there is an urgent unmet need to devise new, safe, and more effective treatment modalities for skin cancers. Herein, a series of flavonol-based derivatives of fisetin, a plant-based flavonoid identified as an anti-tumorigenic agent targeting the mammalian targets of rapamycin (mTOR)-regulated pathways, were synthesized and fully characterized. New potential inhibitors of receptor tyrosine kinases (c-KITs), cyclin-dependent kinase-2 (CDK2), and mTOR, representing attractive therapeutic targets for melanoma and non-melanoma skin cancers (NMSCs) treatment, were identified using inverse-docking, in vitro kinase activity and various cell-based anticancer screening assays. Eleven compounds exhibited significant inhibitory activities greater than the parent molecule against four human skin cancer cell lines, including melanoma (A375 and SK-Mel-28) and NMSCs (A431 and UWBCC1), with IC50 values ranging from 0.12 to 15 μM. Seven compounds were identified as potentially potent single, dual or multi-kinase c-KITs, CDK2, and mTOR kinase inhibitors after inverse-docking and screening against twelve known cancer targets, followed by kinase activity profiling. Moreover, the potent compound F20, and the multi-kinase F9 and F17 targeted compounds, markedly decreased scratch wound closure, colony formation, and heightened expression levels of key cancer-promoting pathway molecular targets c-Kit, CDK2, and mTOR. In addition, these compounds downregulated Bcl-2 levels and upregulated Bax and cleaved caspase-3/7/8 and PARP levels, thus inducing apoptosis of A375 and A431 cells in a dose-dependent manner. Overall, compounds F20, F9 and F17, were identified as promising c-Kit, CDK2 and mTOR inhibitors, worthy of further investigation as therapeutics, or as adjuvants to standard therapies for the control of melanoma and NMSCs.
Mycobactin Analogues with Excellent Pharmacokinetic Profile Demonstrate Potent Antitubercular Specific Activity and Exceptional Efflux Pump Inhibition
Basavanakatti, Vinay N.,Bhakta, Sanjib,Bhattacharje, Gourab,Brucoli, Federico,Das, Amit Kumar,Das, Swetarka,Dasgupta, Arunava,Dev, Abhimanyu,Dickman, Rachael,Jalani, Pushpendu,Jayaprakash, Venkatesan,Kamilya, Sujit,Mondal, Abhishake,Mukherjee, Piyali,Naresh Babu, Patibandla,Sankaran, Vadivelan,Shyam, Mousumi,Singh, Amit,Singh, Samsher,Sinha, Barij Nayan,Verma, Harshita,Bagnéris, Claire
, (2022/01/20)
In this study, we have designed and synthesized pyrazoline analogues that partially mimic the structure of mycobactin, to address the requirement of novel therapeutics to tackle the emerging global challenge of antimicrobial resistance (AMR). Our investigation resulted in the identification of novel lead compounds 44 and 49 as potential mycobactin biosynthesis inhibitors against mycobacteria. Moreover, candidates efficiently eradicated intracellularly surviving mycobacteria. Thermofluorimetric analysis and molecular dynamics simulations suggested that compounds 44 and 49 bind to salicyl-AMP ligase (MbtA), a key enzyme in the mycobactin biosynthetic pathway. To the best of our knowledge, these are the first rationally designed mycobactin inhibitors to demonstrate an excellent in vivo pharmacokinetic profile. In addition, these compounds also exhibited more potent whole-cell efflux pump inhibition than known efflux pump inhibitors verapamil and chlorpromazine. Results from this study pave the way for the development of 3-(2-hydroxyphenyl)-5-(aryl)-pyrazolines as a new weapon against superbug-associated AMR challenges.
