Marine-Inspired Bis-indoles Possessing Antiproliferative Activity against Breast Cancer; Design, Synthesis, and Biological Evaluation.

Diverse indoles and bis-indoles extracted from marine sources have been identified as promising anticancer leads. Herein, we designed and synthesized novel bis-indole series 7a-f and 9a-h as Topsentin and Nortopsentin analogs. Our design is based on replacing the heterocyclic spacer in the natural leads by a more flexible hydrazide linker while sparing the two peripheral indole rings. All the synthesized bis-indoles were examined for their antiproliferative action against human breast cancer (MCF-7 and MDA-MB-231) cell lines. The most potent congeners 7e and 9a against MCF-7 cells (IC50 = 0.44 ± 0.01 and 1.28 ± 0.04 µM, respectively) induced apoptosis in MCF-7 cells (23.7-, and 16.8-fold increase in the total apoptosis percentage) as evident by the externalization of plasma membrane phosphatidylserine detected by Annexin V-FITC/PI assay. This evidence was supported by the Bax/Bcl-2 ratio augmentation (18.65- and 11.1-fold compared to control) with a concomitant increase in the level of caspase-3 (11.7- and 9.5-fold) and p53 (15.4- and 11.75-fold). Both compounds arrested the cell cycle mainly in the G2/M phase. Furthermore, 7e and 9a displayed good selectivity toward tumor cells (S.I. = 38.7 and 18.3), upon testing of their cytotoxicity toward non-tumorigenic breast MCF-10A cells. Finally, compounds 7a, 7b, 7d, 7e, and 9a were examined for their plausible CDK2 inhibitory action. The obtained results (% inhibition range: 16%-58%) unveiled incompetence of the target bis-indoles to inhibit CDK2 significantly. Collectively, these results suggested that herein reported bis-indoles are good lead compounds for further optimization and development as potential efficient anti-breast cancer drugs.

Modified Potentiometric Screen-Printed Electrodes Based on Imprinting Character for Sodium Deoxycholate Determination.

Potentiometric sensors have a great influence on the determination of most various compounds in their matrices. Therefore, efficient and new sensors were introduced to measure sodium Deoxycholate (NaDC) as a bile acid salt. These sensors are based on NaDC imprinted polymer (MIP) as sensory element. The MIP beads were synthesized using thermal polymerization pathway, in which acrylamide (AAm), ethylene glycol dimethacrylate (EGDMA), NaDC, and benzoyl peroxide (BPO) were used as the functional monomer, cross-linker, template, and initiator, respectively. The proposed sensors were fabricated using a coated screen-printed platform and the sensing membrane was modified by single-walled carbon nanotubes (SWCNTs) as an ion-to-electron transducer. The sensors exhibited high sensitivity that reached 4.7 × 10-5 M of near-Nernestian slope (-60.1 ± 0.9 mV/decade, r2 = 0.999 (n= 5)). In addition, the sensors revealed high selectivity, long lifetime, high potential stability, and conductivity that ensure reproducible and accurate results over a long time. MIP characterization was performed using Fourier Transform-Infrared (FT-IR) and a scanning electron microscope (SEM). Regarding the interaction of NaDC with serum albumin (SA), albumin is determined in human serum samples as human serum albumin (HSA), which was collected from different volunteers of different ages and gender.