Studying the chemical modification of cellulose and some cellulose derivatives with their industrial evaluation and environmental application

Abstract

Synthesis of 4-aryl-6-indolylpyridine-2-carbonitriles and evaluation of their biological activity A novel series of 4-aryl-6-indolylnicotinonitrile-2-ones (1a-e) was prepared via the one-pot multicomponent synthesis, in the presence of piperidine as a base catalyst following the microwave irradiation approach and traditional thermal heating approach, scheme 1. O NH CN O EtO + + NH R CN O NH R H (1a-e) O + MWI or thermal heating Scheme 1 1 a b c d e R = 2-C4H3S 4-OCH3C6H4 4-FC6H4 4-ClC6H4 4-BrC6H4 NH4OAc/ piperidine The rate of reaction and the product yield obtained by the microwave irradiation approach were compared to that obtained by the conventional heating method. Under the microwave irradiation, the synthesis was achieved in (15-20) minutes, and the yield was (77-87%). While the synthesis of the same compounds took (10-18) hours under the thermal heating and afforded (44-63%) yield, which was lower than the microwave irradiation method, table 1. English Summary b Compounds (1a-e) were treated with phosphoryl chloride for (18-24) hours at 80 oC under reflux, yielding the 2-chloro- 6-indolylnicotinonitrile derivatives (2a-e), scheme 3. 1,2 a b c d e R = 2-C4H3S 4-OCH3C6H4 4-FC6H4 4-ClC6H4 4-BrC6H4 NH R CN O NH (1a-e) N R CN Cl NH (2a-e) POCl3 ref luxing 18-24 h Scheme 3 Refluxing the 2-chloro-6-indolylnicotinonitriles (2a-e) with ethylene-1,2-diamine for 36-48 h in ethanol using TEA as a base catalyst, yielded the corresponding 2-((2-aminoethyl)- amino)-6-indolylnicotinonitriles (3a-e), scheme 4. 2,3 a b c d e R= 2-C4H3S 4-OCH3C6H4 4-FC6H4 4-ClC6H4 4-BrC6H4 N R CN Cl NH (2a-e) N R CN NH NH (3a-e) H2N NH2 NH2 ET3N, EtOH reflux 36-48 h Scheme 4 All compounds were tested for their anti-proliferative potency on a panel of cancer cell lines including; (SK-OV-3), (MCF-7), and (HeLa) cells. Interestingly, among the tested English Summary c compounds (3a, 3b, 3d, and 3e) were the most active in inhibiting the proliferation of the cancer cells. Interestingly, these four compounds were more potent in SK-OV-3 and MCF-7 cells compared to their activity in HeLa cells, reflecting their cell-specificity, figure 1. The IC50 values for compounds (3a, 3b, 3d, and 3e) also were determined, table 2 and figure 3. Furthermore, compounds (3b, d, and e) were screened for their antimicrobial activities at concentration (2 mg/ mL), by using the well diffusion method against four microbial strains. The three derivatives were active against Bacillus subtilis, and Staphylococcus aureus as examples for gram positive bacteria, and Candida as an example for yeast. However, they did not show any activity against Escherichia coli as an example for gram negative bacteria, table 3. English Summary d Part 2 Grafting of 2-((2-aminoethyl)amino-6-indolyl nicotinonitrile to cellulose tosylate Microcrystaline cellulose MCC with DP 225 was employed to prepare 6-deoxytosyl cellulose TsMCC, with DSTs 0.44. This DSTs value of TsMCC improved cellulose solubility, as it became soluble in DMF, DMA, dioxane, and DMSO, scheme 5. O O HO OH O OH S O O Cl DMA/LiCl (ET)3N, 0-7 oC O O HO OR O S O O O n n Scheme 5 MCC, DP = 225 TsMCC, DSTs= 0.44 R = H, or Ts 2-((2-Aminoethyl)amino)-6-indolylnicotinonitriles (3b, d, and e) which had promising antimicrobial activity, were selected for the grafting of cellulose tosylate via its partial nucleophilic substitution for the tosyl group (Ts is a good leaving group). The reaction was carried out in refluxing DMF at 80oC, and TEA was used as a base catalyst, affording the corresponding novel aminocellulose derivatives (4a-c), scheme 6. English Summary e O O HO OR O n R= H, or Ts TsMCC N R1 NC NH NH H2N N R1 NC NH NH NH O O HO OR n + Scheme 6 (3b, d, e) (4a-c) DMF/ TEA 80 oC with stirring O S O O O 4 a b c R1 = 4-OCH3C6H4 4-ClC6H4 4-BrC6H4 3 b d e R1 = 4-OCH3C6H4 4-ClC6H4 4-BrC6H4 The new aminocellulose derivatives (4a-c) were evaluated for their antimicrobial activity, on four different pathogenic bacterial strains namely; Staphylococcus, and Bacillus subtilis (gram positive), Escherichia coli (gram negative), and Candida (yeast). The results suggested that, the immobilization of the active heterocyclic amines on the surface of tosyl cellulose retarded their antimicrobial performance.