Nitrogen Containing Heterocyclic Compounds-Synthesis And Properties Of Triazine-Stilbene Fluorescent Whitening Agents、Isoxazole Chalcone And Indole Schiff Base Derivatives

Nitrogen-containing heterocyclic compounds are an important part of modern organic chemistry, which have widely infiltrated into many frontier areas such as pharmaceuticals and materials, and become one of the most active contemporary organic synthetic research fields.Fluorescent whitening agents are widely used in many fields, such as industrial and agricultural production and high-tech technology. However, the harm of fluorescent whitening agent products and their production processes to human and environment is also of growing human attention. The molecular structures of fluorescent whitening agents are very complicated, unlike chemical composition easily be broken, fluorescent whitening agents will accumulate in the human body and endanger human health. According to clinical experiments, fluorescent compounds enable cells to generate variability, which may be potential cancer risk. As human quality of life for the pursuit of health and safety, people have a higher fluorescent whitening agent requirements. In all types of fluorescent whitening agent products, triazine-stilbene fluorescent whitening agents have a very important position, accounting for above60%of the number of varieties of fluorescent whitening agents. Triazine-stilbene fluorescent whitening agents as a very important class of photochemical products possess a wide range of applications and good market prospects. However, because of their toxicity, poor light resistance and the decrease of whitening efficiency, their applications and development are limited. Current study in fluorescent whitening agents is mainly the modification of triazine-stilbene fluorescent whitening agents, that is, fluorescent whitening agents with green and multifunction are prepared by grafting different substituents in the parent structure. With economic development and continuous improvement of the quality of human life, the research of fluorescent whitening agents will achieve leapfrog development.Since the twentieth century, cancer has become a major killer of a threat to human life, it’s second only to cardiovascular disease mortality. Therefore, the development of anticancer drugs has become one of the hot spots in the field of pharmaceutical research and development. The biggest drawback of antineoplastic drugs in current clinical use is toxicity and low selectivity. Thus, the synthesis of new anti-cancer drugs with high efficiency, low toxicity and strong selectivity is becoming the direction of research and development. Chalcone and its derivatives are widely found in nature and their parent structure contains1,3-diaryl propenone. Chalcones having a wide range of biological activity, e.g. anti-tumor activity, anti-HIV activity, antibacterial activity, anti-malarial and anti-parasitic activity, are a class of very promising drug template. Further, α, β-enone structure is a soft electrophile and tends to interact mercapto compounds instead of reaction with amino group, hydroxyl group, and nucleic acid, causing mutations or cancer. In the field of medicine, indole derivatives are a very important class of nitrogen-containing heterocyclic compounds and have a good physical activity, such as anti-cancer, anti-bacterial, anti-viral, anti-oxidant and anti-malarial activity and so on. In the design of new drugs, the combination of different pharmacologically interesting monomer may lead to a biologically active compound. Therefore, the design and synthesis with high efficiency and low toxicity of anticancer drugs become one of the most important tasks of chemical and pharmaceutical workers.In this paper, four novel nitrogen-containing heterocyclic compounds including triazine-stilbene-amino acids, triazines-stilbene-dodecyl quaternary ammonium, isoxazolyl chalcones and indole schiff bases were designed and synthesized. The reaction conditions, spectral properties and photophysical properties of target compounds were studied. Their cytotoxicity, antibacterial activity and anti-cancer activity were tested and some compounds with good biological characteristics were found. The details are as follows:1. A series of novel triazine-stilbene-amino acid fluorescent whitening agents were first designed and synthesized. Their physical properties and cytotoxicity were studied. Their stuctures were characterized by1H NMR,13C NMR and IR spectra. The UV absorptions of the compounds were in the range of240-450nm and the absorption peaks of the cis-isomers and trans-isomers were in281-291nm and353-361nm, respectively. The physical property data indicated that all the triazine-stilbene-amino acid fluorescent whitening agents showed excellent whitening effect on cotton fiber compared to untreated cotton. These compounds showed higher washing fastness and higher rubbing fastness. The preliminary cytotoxicity of these derivatives on a mouse fibroblast cell line (L-929cells) was also investigated using MTT assay. The results showed that the compounds7a-h were nontoxic to L-929cells as green fluorescent whitening agents. It is an effective way to synthesis triazine-stilbene-amino acid derivatives, which has the advantages of mild reaction conditions, simple operation and good yields.2. A series of novel triazine-stilbene-dodecyl quaternary ammonium salt fluorescent whitening agents were first designed and synthesized. This synthetic method is an effective way to synthesis triazine-stilbene-long chain alkyl quaternary ammonium salt fluorescent whitening agents with the advantages of mild reaction conditions and good yields. The optical properties of the newly synthesized compounds6a-f were investigated by whiteness measurement and fastness test. Results showed that these compounds showed higher degree of whiteness on pure cotton fiber compared to the untreated, higher washing fastness and higher rubbing fastness. By acid and alkali resistance tests, it is clear that the triazine-stilbene-quaternary ammonium as fluorescent whitening agents had strong acid and alkali resistance. Their antimicrobial activities were confirmed against Streptococcus mutans (UA159), Candida albicans (5313a) and E. coli (ATCC25922) strains. Preliminary structure-activity relationship studies suggested that the introduction of carboxylic group into the stilbene-triazine-quaternary ammonium salt derivatives would significantly enhance their antimicrobial activity.3. A series of novel isoxazolyl chalcones were first synthesized and evaluated for their activities in vitro against four types of human non-small cell lung cancer cells, including H1792, H157, A549and Calu-1cells. It is an effective way to synthesis of isoxazolyl chalcone derivatives with the advantages of mild reaction conditions, simple operation and good yields. The preliminary biological screening showed that compounds5d and5f-i exhibited significant cytotoxicity. Particularly, compounds5f and5h were identified as the most potent anticancer agents with IC50values1.35-2.07μM and7.27-11.07μM against H175, A549and Calu-1cell lines, respectively. Compounds5f-i could induce apoptosis in A549cells by cell cycle and western blot analysis. The preliminary structure-activity relationship study showed that compounds bearing electron withdrawing groups (EWG) at the2-position of the phenyl ring in Ar group were more effective than those with EWG at4-position. These results further demonstrated that the compounds designed in this work might lead to the discovery of novel anti-lung cancer agents.4. A series of novel indole schiff base derivatives4a-i were first synthesized. The isolated compounds were characterized by IR,1H NMR,13C NMR spectra and MS. The cytotoxicity of these compounds against lung cancer cells (H1792, A549, H157and Calu-1cells) was evaluated by a SRB (sulforhodamine B) assay. The results showed that all compounds had almost inhibitory effects on the growth of four different lung cancer cells. Among them, compound3g was the most effective small molecule in inhibiting lung cancer cell growth. It is an effective method for the synthesis of indole schiff base derivatives with the advantages of easily accessible starting material, straight forward product isolation and good yields.