Today, one of the most important challenges for physicians is the adequate treatment of infections due to multidrug resistant organism (MDR). Pseudomonas aeruginosa is considered an opportunistic organism causing different types of healthcare associated infections (HAIs). We aimed to investigate the MDR and pandrug resistance (PDR) rate in P. aeruginosa in our region and detect efflux-pump mexAB genes and the proposed binding interactions of five different categories of antimicrobial agents with the mexB pump. A total of 180 non-duplicated P. aeruginosa strains were isolated from patients with HAIs in the Suez Canal University Hospital. Phenotypically, minimum inhibitory concentration (MIC) was done for all MDR and PDR strains before and after addition of efflux pump inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Molecular detection of mexA and mexB genes was done by using polymerase chain reaction (PCR). Most of the isolated strains (126 strains) were MDR (70%); only 10 samples (5.5%) were PDR. MexA and mexB genes were detected in 88.2% (120 strains) and 70.5% (96 strains) of stains, respectively. All PDR strains (10 stains) carried both mexA and mexB genes. Efflux mexAB genes were detected in all MDR and PDR strains (136 strains). Molecular modeling studies were performed to investigate the modes of intermolecular binding interactions between the antimicrobial agents and mexB key amino acids that resulted in MDR and PDR. The current study reported high prevalence of MDR and PDR P. aeruginosa in patients with HAIs in the Suez Canal University Hospitals.

The emergence of untreatable drug‐resistant strains of Mycobacterium tuberculosis is a major public health problem worldwide, and the identification of new efficient treatments is urgently needed. Mycobacterium tuberculosis cytochrome P450 CYP121A1 is a promising drug target for the treatment of tuberculosis owing to its essential role in mycobacterial growth. Using a rational approach, which includes molecular modelling studies, three series of azole pyrazole derivatives were designed through two synthetic pathways. The synthesized compounds were biologically evaluated for their inhibitory activity towards M. tuberculosis and their protein binding affinity ( K D ). Series 3 biarylpyrazole imidazole derivatives were the most effective with the isobutyl ( 10 f ) and tert ‐butyl ( 10 g ) compounds displaying optimal activity (MIC 1.562 μg/mL, K D 0.22 μM ( 10 f ) and 4.81 μM ( 10 g )). The spectroscopic data showed that all the synthesised compounds produced a type II red shift of the heme Soret band indicating either direct binding to heme iron or (where less extensive Soret shifts are observed) putative indirect binding via an interstitial water molecule. Evaluation of biological and physicochemical properties identified the following as requirements for activity: LogP >4, H‐bond acceptors/H‐bond donors 4/0, number of rotatable bonds 5–6, molecular volume >340 Å 3 , topological polar surface area <40 Å 2 .

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), which caused novel corona virus disease-2019 (COVID-19) pandemic, necessitated a global demand for studies related to genes and enzymes of SARS-CoV2. SARS-CoV2 infection depends on the host cell Angiotensin-Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease-2 (TMPRSS2), where the virus uses ACE2 for entry and TMPRSS2 for S protein priming. The TMPRSS2 gene encodes a Transmembrane Protease Serine-2 protein (TMPS2) that belongs to the serine protease family. There is no crystal structure available for TMPS2, therefore, a homology model was required to establish a putative 3D structure for the enzyme. A homology model was constructed using SWISS-MODEL and evaluations were performed through Ramachandran plots, Verify 3D and Protein Statistical Analysis (ProSA). Molecular dynamics simulations were employed to investigate the stability of the constructed model. Docking of TMPS2 inhibitors, camostat, nafamostat, gabexate, and sivelestat, using Molecular Operating Environment (MOE) software, into the constructed model was performed and the protein-ligand complexes were subjected to MD simulations and computational binding affinity calculations. These in silico studies determined the tertiary structure of TMPS2 amino acid sequence and predicted how ligands bind to the model, which is important for drug development for the prevention and treatment of COVID-19.

Quinoline-based thiazolidinone heterocycles exhibited potent activity in the field of cancer therapy. Hence, ten quinoline-based thiazolidinone derivatives were evaluated for their anticancer activity through cytotoxic activity, epidermal growth factor receptor (EGFR) inhibition pathway, apoptosis investigation through flow cytometric analyses, RT-PCR gene expression, in vivo solid-Ehrlich carcinoma model, and finally in silico approach for highlighting the interaction pose. Results revealed that compound 7 exhibited cytotoxic activity against HCT-116 cells with an IC 50 value of 7.43 µM compared to 5-FU (IC 50 = 11.36 µM) with moderate cytotoxic activity against the FHC (IC 50 = 35.27 µM), and it exhibited remarkable inhibition activity of EGFR with IC 50 value of 96.43 nM compared to Erlotinib (IC 50 = 78.65 nM). Moreover, it significantly stimulated apoptotic colon cancer cell death with 171.58-fold arresting cell cycle at G2 and S-phases.Additionally, it ameliorated both biochemical and histochemical structures near normal with tumor inhibition ratio of 52.92% compared to 5-FU of 57.16%, with immunohistochemical examinations of EGFR inhibition in the treated group compared to control. Finally, molecular docking study highlighted its good binding affinity through good interactive binding pose inside the EGFR protein. In conclusion, the potent EGFR inhibitory activity of compound 7 was investigated using three integrated approaches in vitro, in vivo, and in silico, so it worth be validated and developed as a chemotherapeutic anticancer agent.