Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Discovery of New 1,4,6-Trisubstituted-1H-pyrazolo[3,4-b]pyridines with Anti-Tumor Efficacy in Mouse Model of Breast Cancer
Δημιουργός/Συγγραφέας:	Georgiou, Maria Lougiakis, Nikolaos Tenta, Roxane Gioti, Katerina Baritaki, Stavroula Gkaralea, Lydia-Evangelia Deligianni, Elisavet Marakos, Panagiotis Pouli, Nicole [EL] Στέλλας, Δημήτρης[EN] Stellas, Dimitris
Ημερομηνία:	2023-02-27
Γλώσσα:	Αγγλικά
ISSN:	1999-4923
DOI:	10.3390/pharmaceutics15030787
Άλλο:	36986648
Περίληψη:	Purine analogues are important therapeutic tools due to their affinity to enzymes or receptors that are involved in critical biological processes. In this study, new 1,4,6-trisubstituted pyrazolo[3,4-b]pyridines were designed and synthesized, and their cytotoxic potential was been studied. The new derivatives were prepared through suitable arylhydrazines, and upon successive conversion first to aminopyrazoles, they were converted then to 1,6-disubstituted pyrazolo[3,4-b]pyridine-4-ones; this served as the starting point for the synthesis of the target compounds. The cytotoxic activity of the derivatives was evaluated against several human and murine cancer cell lines. Substantial structure activity relationships (SARs) could be extracted, mainly concerning the 4-alkylaminoethyl ethers, which showed potent in vitro antiproliferative activity in the low μM level (0.75-4.15 μΜ) without affecting the proliferation of normal cells. The most potent analogues underwent in vivo evaluation and were found to inhibit tumor growth in vivo in an orthotopic breast cancer mouse model. The novel compounds exhibited no systemic toxicity; they affected only the implanted tumors and did not interfere with the immune system of the animals. Our results revealed a very potent novel compound which could be an ideal lead for the discovery of promising anti-tumor agents, and could also be further explored for combination treatments with immunotherapeutic drugs.
Τίτλος πηγής δημοσίευσης:	Pharmaceutics
Τόμος/Κεφάλαιο:	15
Τεύχος:	3
Θεματική Κατηγορία:	[EL] Κυτταρολογία[EN] Cytology [EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) [EL] Βιοχημεία[EN] Biochemistry [EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	anticancer agent antiproliferative activity breast cancer in vivo purine analogues pyrazolopyridine
Κάτοχος πνευματικών δικαιωμάτων:	© 2023 by the authors. Licensee MDPI, Basel, Switzerland.
Όροι και προϋποθέσεις δικαιωμάτων:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.3390/pharmaceutics15030787
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο