Development of Promising Thiopyrimidine-Based Anti-cancer and Antimicrobial Agents: Synthesis and QSAR Analysis

Abstract

New hybrids of thiopyrimidine-five/six heterocyclic rings were synthesized and in vitro evaluated for their antiproliferative activity against three human cancer cell lines, namely HCT116 (human colorectal carcinoma), PC-3 (human prostate adenocarcinoma) and HepG2 (human liver carcinoma) cell lines. The most potency was elicited by the target candidates against the viability of HCT116 cell lines, higher than the positive control 5-Fluorouracil (IC50 range; 0.11-0.49 µM, IC50, 5-FU; 1.10 µM). Cell cycle analysis and apoptosis activation revealed that compound 20 induced G2/M phase arrest and apoptosis in HCT116 cells. In addition, 20 activates the caspases-9 and -3, a process which might mediate the apoptosis of HCT116 cells. Quantitative structure activity relationship study was done and revealed a high predictive power R2 suggesting goodness of the models. Furthermore, there is a good agreement between the observed pIC50 and the predicted pIC50 values, in addition, the low RMSD and standard error values indicate the accuracy of the model. Antimicrobial evaluation revealed that some of these compounds exhibited significant activities against the tested pathogenic bacteria and fungi, wherein compounds 7a, 14, 15a, 21a, produced the most potent and broad spectrum antibacterial and antifungal potency equivalent to that revealed by Vibramycin and Ketoconazole (MIC; 125 μg/mL). Moreover, compounds 15a, 21c, investigated dual potent antimicrobial and anticancer activity.

Synthesis and biological evaluation of new derivatives of thieno-thiazole and dihydrothiazolo-thiazole scaffolds integrated with a pyrazoline nucleus as anticancer and multi-targeting kinase inhibitors

“…The biological potential of the newly prepared target structures was inspected toward the examined organisms and expressed as the diameter of the inhibition zones due to the agar plate diffusion technique. [64][65][66][67][68][69] More details in the ESI. † 2.2.5.1.…”

Green Synthesis of Curcumin Derivatives with Expected Biological Activities as Potential Antitumor, Radical Scavenging Agents and Their Applications Antibacterial Wound Dressings

“…The anti-proliferative activities on the RPE-1 and MCF-7 human cell types were assessed by the 3-[4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. This assay is grounded on the cleavage of the tetrazolium salt by the viable cells' mitochondrial dehydrogenases [26][27][28][29] . The cells were distributed in a 96 well sterile microplate (5 x 10 4 cells/well), then incubated for 48 h in a serum free medium at 37 o C with concentration series, in DMSO, of each compound or doxorubicin ® as positive control prior to the MTT assay.…”

Convenient synthesis of new indeno[1,2-b]pyridine derivatives for antimicrobial and antioxidant evaluation

“…Based on the aforementioned findings, and in continuation of our previous efforts to find out new potent antimicrobial and antioxidant agents aiming to combat the microbial resistance problem [14][15][16][17], this study deals with synthesis of two series of novel rigid analogs bearing 4-(4-hydroxy-3-methoxyphenyl)-2oxo-2,3-dihydro-1H-indeno [1,2-b]pyridine-3-carbonitrile scaffold which is either conjugated with different heterocyclic rings at pyridine-2-position via an oxyacetamide linker or alkylated with different substituted alkyl chains at pyridine-N1-position. The structural formulae of the new derivatives were confirmed using microanalytical and spectral data.…”