Optimization of (Phenylmethylidene)‐hydantoins as Prostate Cancer Migration Inhibitors: SAR‐Directed Design,Synthesis, and Pharmacophore Modeling

Prostate cancer is one of the most common cancer forms among males of Western countries. Natural products proved to be an unparalleled source of molecular diversity. The 4‐(hydroxyphenylmethylidene)hydantoin (PMH; 1 ), (5Z)‐5‐(4‐hydroxybenzylidene)imidazolidine‐2,4‐dione, was isolated from the Red Sea sponge Hemimycale arabica, and recently showed junctional complexes stabilization, anti‐invasive, and antimetastatic activities in vitro and in vivo. The related synthetic analogue, (5Z)‐5‐[4‐(ethylsulfanyl)benzylidene]imidazolidine‐2,4‐dione ( 2 ), showed several‐fold‐improved in vivo antimetastatic properties against the highly invasive prostate cancer. To further optimize the activity of PMHs, various ligand‐based strategies were used including the extension of the structure, structural simplification, linker extension, and computer‐assisted CoMFA (Comparative Molecular Field Analysis) results. These strategies yielded thirty 2nd‐generation PMHs, designed based on the 1st‐generation PMHs, such as 1 and 2 . Wound‐healing assay was selected to evaluate the in vitro anti‐migratory potential of these new PMHs against the PC‐3 cell line. Several active PMHs, including 10, 13, 24, 29 , with nearly twelvefold enhancement of activity vs. 2 , were identified. Active compounds were then used to build a pharmacophore model using the SYBYL's DIStance COmparison technique (DISCOtech). Active PMHs were also screened for fragment‐based drug likeness using the OSIRIS program, and an overall drug score was also calculated. Interestingly, the overall drug scores of 24 and 29 along with their anti‐migratory activity were significantly greater than those of 1 and 2 . In conclusion, PMHs can be the appropriate scaffolds for the urgently needed drug candidates for the control of androgen independent prostate cancer.     

Utilization of erythrosine B in spectrofluorimetric quenching analysis of amlodipine and perindopril in pharmaceutical and biological matrices

A spectrofluorimetric approach that is sensitive, simple, validated, and cost-effective has been proposed for the estimation of amlodipine (AML) and perindopril (PER) in their bulk powders, pharmaceutical formulations, and spiked human plasma. The recommended approach utilized the quantitative quenching effect of the two cited drugs on the fluorescence intensity of erythrosine B, as a result of complex binary reactions among each drug with erythrosine B at pH 3.5 (Teorell and Stenhagen buffer). The quenching of erythrosine B fluorescence was recorded at 554 nm after excitation at 527 nm. The calibration curve was detected in the range 0.25–3.0 μg ml⁻¹, with a correlation coefficient of 0.9996 for AML, and 0.1–1.5 μg ml⁻¹, with a correlation coefficient of 0.9996 for PER. The established spectrofluorimetric approach was validated for the estimation of the cited drugs with high sensitivity regarding International Council on Harmonization guidelines. Therefore, the established approach could be utilized for quality control of the cited drugs in their pharmaceutical formulations.     

Genetic variability of the tropical grasshopper Poecilocerus bufonius in Saudi Arabia

Electrophoresis for SDS-proteins and isoenzymes was applied to investigate the genetic variability within the tropical grasshopper Poecilocerus bufonius, which inhabits Saudi Arabia. Samples were selected from different localities that are encompassing the Sarawat Mountains in the west and An-Nafud desert in the north and middle. A range of 2 to 14 protein bands were recorded in the studied samples as measured by SDS-polyacrylamide gel electrophoresis, from which only two were common. The maximum number of protein bands has been recorded in the samples from the west and the minimum number has been recorded in the samples from the north and middle. Six arbitrary chosen enzymes were examined by native-polyacrylamide gel electrophoresis. They were peroxidase (Px), aldehyde oxidase (Ao), acid phosphatase (Acph), alcohol dehydrogenase (Adh), á and â ePsterase (Est). Fourteen presumptive gene loci and 26 polymorphic alleles have been recorded with the highest number of alleles in Taif and minimum number of alleles in Qassim. Adh, Px and Acph have not been recorded in samples from the localities of An-Nafud desert. The samples from Taif (Sarawat Mountains) were more genetically variable than the samples from other localities. Most of alleles were monomeric but only the Px-1 showed trimeric alleles in samples from Taif.     

Pathogenic LMNA variants disrupt cardiac lamina-chromatin interactions and de-repress alternative fate genes

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Ipomoea staphylina Attenuates Potassium Dichromate-Induced Nephrotoxicity in Wistar Rats via Antioxidant and Antiapoptotic Effects

Doklady Biochemistry and Biophysics - Occupational and environmental exposure to chromium compounds leads to nephrotoxicity to humans and animals due to the overproduction of ROS. Our study was...