Xiaoping Zhan

Synthesis, Cytotoxic, and Antibacterial Evaluation of Quinazolinone Derivatives with Substituted Amino Moiety

A series of novel quinazolinone derivatives containing a substituted amino moiety were synthesized, evaluated for their cytotoxic and antibacterial activities. The results of MTT assay showed that all synthesized target compounds 5A – 5O showed potent cytotoxicity against SGC‐7901 (IC50, 0.72 – 1.41 μm). Moreover, the compounds 5D, 5I, and 5K showed better selectivity as compared with positive controls pemetrexed and MTX due to weak cytotoxicity against normal tissue cell line HUVSMC. Among synthesized compounds, the compounds 5E, 5J, 5L, and 5N showed broad‐spectrum cytotoxic activities against at least four cancer cell lines at a micromolar level. The results of antibacteria evaluation revealed that all synthesized compounds showed good to moderate antibacterial activities against Gram‐negative bacteria Escherichia coli. Among them, the MIC values of the compounds 5C, 5F, and 5M were 0.31 μg/mL.

Acrylate copolymer: a rate-controlling membrane in the transdermal drug delivery system

Abstract A film-like copolymer composed of 2-hydroxy-3-phenoxypropylacrylate, 4-hydroxybutyl acrylate and cyclohexyl methacrylate was synthesized and exploited as a rate-controlling membrane in the transdermal drug delivery systems (TDDs). A series of acrylate copolymers with different formulations were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry and tensile strength, and then evaluated by clonidine hydrochloride transporting through the films. It was found that the formulation M2 composed of three monomers at a ratio of 4:4:2 (w/w/w) showed excellent mechanical and permeation properties. The optimal formulation M2 was further characterized by scanning electron microscopy, contact angles and swelling ratio, and then the permeation behaviors of five different physicochemical drugs transporting through the M2 were evaluated. The results showed that the permeation behaviors were influenced by many factors including the thickness of the membrane, the physicochemical properties of the drugs, the dose of the drugs and the interactions between the drugs and the membrane. This type of copolymer membrane might open new applications in the field of TDDs.

Synthesis and Biological Evaluation of 3-Substituted-4-(4-methylthio phenyl)-1HPyrrole Derivatives as Potential Anticancer Agents

A novel series of 3-substituted-4-(4-methylthio phenyl)-1H-pyrrole derivatives were synthesized via Van Leusen pyrrole synthesis. The in vitro anticancer activity against a panel of 16 cancer cell lines and 2 normal cell lines was investigated by MTT assay. It was found that some of the pyrrole compounds showed similar antiproliferative activity against cancer cells compared with Paclitaxel, but little impact on normal cell lines, which indicated that the novel pyrrole derivatives could be used as potential anticancer candidates for possessing both selectivity and good therapeutic efficacy. Structure-activity relationship analysis found that 3-phenylacetyl-4- (4-methylthio phenyl)-1H-pyrrole derivatives displayed the most strong anticancer activity, among which [4-(4-methylthio phenyl)-1Hpyrrol- 3-yl] (4-methoxy phenyl) methanone (3j) was employed to investigate the effect of these pyrrole analogues on cell cycle by propidium iodide (PI) staining on cell flow cytometry. Cell necrotic effect of 10.0 µM 3j against MGC80-3 cells were also observed under fluorescence microscope and transmission electron microscope by ultrathin sections observation.

Synthesis, characterization and molecular dynamics simulation of the polyacrylates membranes

Abstract The aims of this paper are to investigate the inherent relationship between the structures of the polyacrylates and release behaviors as drug carriers in the transdermal drug delivery systems. Three model polyacrylates compounds were synthesized by radical polymerization. Three polymer materials were characterized by Fourier transform infrared, differential scanning calorimeter and cytotoxicity, and the release behaviors of drug molecules transporting through the polymers membranes were tested. Moreover, the effects of the polymers’ structures on the permeability were studied by molecular dynamic simulation. The simulation results showed that higher chains mobility and larger fractional free volume of the polymer membranes resulted in higher permeation rates. By comparing the monomers’ structure in the polymer materials, it was found that the polymer chains’ mobility decreases, and permeation rate correspondingly decreases with the increase in the amount and volume of side groups on the double bonds.

Synthesis and anticancer activity of 3-(substituted aroyl)-4-(3,4,5-trimethoxy phenyl)-1H-pyrrole derivatives

A series of 3‐(substituted aroyl)‐4‐(3,4,5‐trimethoxyphenyl)‐1H‐pyrrole derivatives were synthesized and determined for their anticancer activity against eleven cancer cell lines and two normal tissue cell lines using MTT assay. Among the synthesized compounds, compound 3f was the most potent compound against A375, CT‐26, HeLa, MGC80‐3, NCI‐H460 and SGC‐7901 cells (IC50 = 8.2 – 31.7 μm); 3g, 3n and 3a were the most potent compounds against CHO (IC50 = 8.2 μm), HCT‐15 (IC50 = 21 μm) and MCF‐7 cells (IC50 = 18.7 μm), respectively. Importantly, all the target compounds showed no cytotoxicity towards the normal tissue cell (IC50 > 100 μm). Thus, these compounds with the potent anticancer activity and low toxicity have potential for the development of new anticancer chemotherapy agents.

Synthesis and Anti-cancer Activity of 3-substituted Benzoyl-4-substituted Phenyl-1H-pyrrole Derivatives

BACKGROUND Cancer is considered a major public health problem worldwide. OBJECTIVE The aim of this paper is to design and synthesis of novel anticancer agents with potent anticancer activity and minimum side effects. METHOD A series of pyrrole derivatives were synthesized, their anti-cancer activity against nine cancer cell lines and two non-cancer cell lines were evaluated by MTT assay, and their cell cycle progression were determined by flow cytometry analysis. RESULTS The study of the structure-activity relationships revealed that the introduction of the electron-donation groups at the 4th position of the pyrrole ring increased the anti-cancer activity. Among the synthesized compounds, specially the compounds bearing 3,4-dimethoxy phenyl at the 4th position of the pyrrole ring showed potent anti-cancer activity, cpd 19 was the most potent against MGC 80-3, HCT-116 and CHO cell lines (IC50s = 1.0－1.7 μM), cpd 21 was the most potent against HepG2, DU145 and CT-26 cell lines (IC50s = 0.5－0.9 μM), and cpd 15 was the most potent against A549 (IC50 = 3.6 μM). Moreover, these potent compounds showed weak cytotoxicity against HUVEC and NIH/3T3. Thus, the cpds 15, 19 and 21 show potential anti-cancer for further investigation. Furthermore, the flow cytometry analysis revealed that cpd 21 arrested the CT-26 cells at S phase, and induced the cell apoptosis. CONCLUSION Thus, these compounds with the potent anticancer activity and low toxicity have potential for the development of new anticancer chemotherapy agents.