Σύνθεση νέων αναλόγων κουμαρινών και αξιολόγηση της βιοδραστικότητάς τους [article]

Filippa-Maria Marinou, National Technological University Of Athens
2020
υ νθεςη νε ων αναλο γων κουμαρινω ν και αξιολο γηςη τησ βιοδραςτικο τητα σ τουσ» Διπλωματική εργαςία Φιλίππα-Μαρία Μαρίνου Επιβλϋπουςα Αναςταςύα Δϋτςη Αναπληρώτρια Καθηγότρια Ε.Μ.Π. Αθήνα 2020 Σχήμα 2. Ακετυλοξυ-κουμαρύνεσ που εμφϊνιςαν το καλϑτερο προφύλ φαρμακο-ομοιϐτητασ Σα υδροξυ-κουμαρινικϊ παρϊγωγα ςτην πλειονϐτητϊ τουσ εμφϊνιςαν εξαιρετικό ικανϐτητα δϋςμευςησ τησ ρύζασ DPPH, εξαιτύασ του κατεχολικοϑ ςυςτόματοσ που διαθϋτουν, καθώσ και ςημαντικό ικανϐτητα αναςτολόσ τησ λιπιδικόσ
more » ... λιπιδικόσ υπεροξεύδωςησ (AAPH). Επομϋνωσ, εμφανώσ μεγαλϑτερη αντιοξειδωτκό δρϊςη εμφϊνιςαν μϋςω DPPH η 4j (IC50=5.3 μΜ) και η 4i (IC50=8.7 μΜ), ενώ μϋςω AAPH η 4g (78%) και η 4i (78%). Σϋλοσ, τη μεγαλϑτερη ικανϐτητα αναςτολόσ τησ δρϊςησ τησ λιποξυγονϊςησ εμφϊνιςαν η 4i (IC50=52 μΜ) και η 4j (IC50=52.5 μΜ). Σχήμα 3. Τδροξυ-κουμαρύνεσ που εμφϊνιςαν την υψηλϐτερη βιοδραςτικϐτητα Καταλόγοντασ, παρατηρόθηκε πωσ τϐςο οι διαφορετικϋσ υποκαταςτϊςεισ ςτον φαινολικϐ δακτϑλιο τησ θϋςησ 3-του κουμαρινικοϑ ςκελετοϑ, ϐςο και οι διαφορετικϋσ θϋςεισ υποκατϊςταςησ ςτο φαινϑλιο, επηρϋαςαν τη βιολογικό δρϊςη των κουμαρινών. Επιςτημονική περιοχή: Οργανικό ςϑνθεςη και αξιολϐγηςη βιοδραςτικϐτητασ. Λέξεισ κλειδιά: κουμαρύνεσ, ακετυλοξυ-κουμαρινικϊ παρϊγωγα, υδροξυκουμαρινικϊ παρϊγωγα, βιοδραςτικϐτητα, αντιοξειδωτικό δρϊςη, αντιφλεγμονώδησ δρϊςη, φαρμακο-ομοιϐτητα 4 ABSTRACT Coumarins are heterocyclic organic compounds, widely found in the plant kingdom and they belong to the benzopyrone family. Both plant-derived and synthetic coumarin derivatives exhibit a remarkable variety of biological properties, such as antioxidant, anti-cancer, antiviral, anticoagulant and anti-inflammatory. The purpose of this thesis was to design, synthesize and characterize novel acetyloxyand hydroxy-coumarin analogues, as well as to evaluate their antioxidant and antiinflammatory activity in specific in vitro bioassays. Specifically, during this work, a total of 22 novel coumarin analogues were synthesized and their structure was identified by 1 H NMR spectroscopy. The 2,3,4-trihydroxyacetophenone constituted the starting material in the modified Perkin reaction used to synthesize the 11 acetyloxy coumarin derivatives. The yields were satisfactory and these compounds were purified by recrystallization. Finally, the 11 acetyloxy coumarins were deacetylated, leading to the 11 hydroxy coumarin analogues, which were synthesized in high yields and did not require purification. The novel acetyloxy coumarin analogues were evaluated for their antioxidant activity through the DPPH and AAPH assays, but also for their ability to inhibit soybean lipoxygenase activity (LOX). The results of this study are indicative of their antiinflammatory activity. After studying the results, it was observed that the acetyloxy-coumarin derivatives didn't exhibit free DPPH radical scavenging capacity, however, they exhibited significant antioxidant activity through the AAPH method. The highest activity was observed for the derivatives 3d (95.3% 100µM) and 3j (95.1% 100µM). In addition, 3g (IC50=19 μΜ) had the strongest anti-inflammatory activity. Scientific area: Organic synthesis and bioactivity evaluation.
doi:10.26240/heal.ntua.18855 fatcat:5cniftmuuzdhnbwrvrkye6mnxa