Synthesis and antimicrobial evaluation of some new quinazolin-4(3H)-one derivatives

The oxazolone derivative 1 was synthesized and converted into a hitherto 3,1-benzoxazin-4-one derivative, 3. A series of quinazolin-4-one derivatives 4a-c and 7-11, as well as quinolinone-3-carboxylic acid derivative, 6, and the amide derivatives, 5a,b, were also synthesized via the 3,1-benzoxazin-4-one derivative. The antimicrobial activity of some of the synthesized compounds was examined against three Gram-positive bacteria (Staphylococcus aureus, Streptococcus mutans and Bacillus subtilis), five Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis and Acinetobacter baumannii) and one fungi (Candida albicans), using diffusion method. The results showed that compounds 4a, 7, 10 and 11 exhibited significant antibacterial and antifungal activity comparable to standard drugs

Synthesis of novel pyrimidine and fused pyrimidine derivatives

4-Amino-2-(benzylthio)-6-(4-methoxyphenyl)pyrimidine-5-carbonitrile (1) was prepared by treatment of s-benzylthiuronium chloride with 2-(4-methoxybenzylidene)malononitrile in ethanolic sodium hydroxide with hydrazine hydrate to afford the hydrazino derivative 2, which was allowed to react with different electrophilic reagents to give the pyrimidine derivatives 3-12. The proclivity of (E)-2-cyano-3-(4-nitrophenyl)acrylamide (13) towards carbon and nitrogen nucleophiles was also investigated. IR, 1H NMR and mass spectra for all the synthesized compounds were discussed. All derived compounds were investigated for anti avian influenza (H5N1) virus activity and compared with zanamivir as control drug. All the synthesized compounds didn’t possess any antiviral activity

Synthesis of 4-aryl-6-indolylpyridine-3-carbonitriles and Evaluation of Their Antiproliferative Activity data files

https://digitalcommons.chapman.edu/pharmacy_data/1001/thumbnail.jp

Synthesis of 4-aryl-6-indolylpyridine-3-carbonitriles and evaluation of their antiproliferative activity

A novel class of 6-indolypyridine-3-carbonitrile derivatives were synthesized and evaluated for antiproliferative activities to establish structure–activity relationship. The synthesis was carried out through one-pot multicomponent reaction of 3-acetylindole, aromatic aldehydes, ethyl cyanoacetate, and ammonium acetate in the presence of piperidine as a catalyst, using a microwave irradiation method or a traditional thermal method. This was followed by chlorination for compounds 13a–e and subsequent nucleophilic substitution of the chlorine group by ethylenediamine at C2 position of the pyridine ring. The antiproliferative activity of these new nicotinonitriles was evaluated against human ovarian adenocarcinoma (SK-OV-3), breast adenocarcinoma (MCF-7), and cervix adenocarcinoma (HeLa) cells. Among all compounds, 2-((2-aminoethyl)amino)-4-aryl-6-indolylnicotinonitriles series (15a, 15b, 15d, and 15e) exhibited higher antiproliferative activity on the three cancer cell lines with IC50 values of 4.1–13.4 μM. [Refer to PDF for graphical abstract

Synthesis of 4-aryl-6-indolylpyridine-3-carbonitriles and Evaluation of Their Antiproliferative Activity

A novel class of 6-indolypyridine-3-carbonitrile derivatives were synthesized and evaluated for antiproliferative activities to establish structure–activity relationship. The synthesis was carried out through one-pot multicomponent reaction of 3-acetylindole, aromatic aldehydes, ethyl cyanoacetate, and ammonium acetate in the presence of piperidine as a catalyst, using a microwave irradiation method or a traditional thermal method. This was followed by chlorination for compounds 13a–e and subsequent nucleophilic substitution of the chlorine group by ethylenediamine at C2 position of the pyridine ring. The antiproliferative activity of these new nicotinonitriles was evaluated against human ovarian adenocarcinoma (SK-OV-3), breast adenocarcinoma (MCF-7), and cervix adenocarcinoma (HeLa) cells. Among all compounds, 2-((2-aminoethyl)amino)-4-aryl-6-indolylnicotinonitriles series (15a, 15b, 15d, and 15e) exhibited higher antiproliferative activity on the three cancer cell lines with IC50 values of 4.1–13.4 μM

Design, Synthesis, and Evaluation of Chitosan Conjugated GGRGDSK Peptides as a Cancer Cell-Targeting Molecular Transporter

Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using (sulfo-SMCC) bifunctional linker affording COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR, 1H NMR, 13C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1 mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of cell-impermeable cargoes (e.g., FAM and F′-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian carcinoma (SK-OV-3) cancer cell lines. Additionally, RGD modified and unmodified COS polymers were used to prepare nanoparticles by ionic gelation and showed particle size ranging from 187 to 338 mm, and zeta potential of 12.2–18.3 mV using dynamic light scattering. The efficiency of COS-NPs and COS-SMCC-RGDSK NPs was assayed for translocation of two synthetic cytotoxic agents ((2-(2-aminoethylamino)-4-(4-chlorophenyl)-6-(1H-indol-3-yl) nicotinonitrile (ACIN), and 2-(2-aminoethylamino)-6-(1H-indol-3-yl)-4-(4-methoxyphenyl)-nicotinonitrile (AMIN)) into CCRF-CEM and human prostate (DU-145) cancer cell lines. The results showed a dramatic reduction in the cell viability on their treatment with RGD targeted COS NPs in comparison to paclitaxel (PTX), free drug, and drug-loaded COS NPs