Eleven 3-amino-2-methyl-quinazolin-4(3H)-ones have been synthesized, in good to excellent yields, via their corresponding benzoxazinones using an efficient tandem microwave-assisted green process. Representative acetamides have been thermally derived from their functional free 3-amino group, whereas for the synthesis of various arylamides, a novel green microwave-assisted protocol has been developed, which involved the attack of hydrazides on benzoxazinones. Eight out of the eleven 3-amino-2-methyl-quinazolin-4(3H)-ones were found photo-active towards plasmid DNA under UVB, and four under UVA irradiation. Amongst all acetamides, only the 6-nitro derivative retained activity both under UVB and UVA irradiation, whereas the 6-bromo-substituted one was active only under UVB. 3-arylamido-6-bromo derivatives exhibited dramatically decreased photo-activity; however, all 3-arylamido-6-nitro compounds developed extraordinary activity, even at concentrations as low as 1μM, which was enhanced compared to their parent 3-amino-2-methyl-6-nitro-quinazolinone. Molecular docking studies were indicative of satisfactory binding to DNA and correlated to the presented photo-activity. Since quinazolinones are known “privileged” pharmacophores for anticancer and antimicrobial activities, the present study gives information on turning “on” and “off” photosensitization on various derivatives which are often used as synthones for drug development, when chromophores and auxochromes are incorporated or being functionalized. Thus, certain compounds may lead to the development of novel photo-chemo or photodynamic therapeutics.

The extraction of valuable phytochemicals from natural sources is an important and constantly evolving research area. Zingiber officinale Roscoe (ginger) contains high amounts of bioactive phytochemicals, which are desirable due to their significant properties. In this work, the ability of different natural deep eutectic solvents (NaDESs) to serve as green solvents for the preparation of high added value extracts from ginger is explored, in combination with ultrasound assisted extraction. The method was optimized by applying a response surface methodology using the NaDES Bet/La/W (1:2:2.5). Three independent variables, namely the extraction time, ultrasound power and NaDES-to-dry-ginger ratio, were investigated by employing a 17-run three-level Box–Behnken Design (BBD) in order to study the correlation between the extraction conditions and the quality of the obtained extracts. The optimum conditions (in order to achieve simultaneously maximum total phenolic content and antioxidant activity), were found to be 23.8 min extraction time, 60 Watt and NaDES/ginger 25:1 w/w. In the optimum conditions the DPPH radical scavenging ability of the extracts was found to reach IC50 = 18.16 mg/mL after 120 min, whereas the TPC was 20.10 ± 0.26 mg GAE/g of dry ginger. The green methodology was also compared with the extraction using conventional solvents. All the obtained extracts were evaluated for their antioxidant activity and their total phenolic content, while the extract derived by the optimum extraction conditions was further investigated for its ability to bind to calf thymus DNA (ctDNA).

Tyrosol, a natural product present in olive oil and white wine, possesses a wide range of bioactivity. The aim of this study was to optimize the preparation of nanosystems encapsulating tyrosol in carbohydrate matrices and the investigation of their ability to bind with DNA. The first encapsulation matrix of choice was chitosan using the ionic gelation method. The second matrix was β-cyclodextrin (βCD) using the kneading method. Coating of the tyrosol-βCD ICs with chitosan resulted in a third nanosystem with very interesting properties. Optimal preparation parameters of each nanosystem were obtained through two three-factor, three-level Box-Behnken experimental designs and statistical analysis of the results. Thereafter, the nanoparticles were evaluated for their physical and thermal characteristics using several techniques (DLS, NMR, FT-IR, DSC, TGA). The study was completed with the investigation of the impact of the encapsulation on the ability of tyrosol to bind to calf thymus DNA. The results revealed that tyrosol and all the studied systems bind to the minor groove of ctDNA. Tyrosol interacts with ctDNA via hydrogen bond formation, as predicted via molecular modeling studies and corroborated by the experiments. The tyrosol-chitosan nanosystem does not show any binding to ctDNA whereas the βCD inclusion complex shows analogous interaction with that of free tyrosol.