Novel 5-amino-1,2,4-triazole derivatives and their cyclized 1,2,4-triazolo[1,5-a]pyrimidine analogues were
designed, synthesized and evaluated for their antimicrobial activities. They were tested against five bacterial
strains (Methicillin Resistant S. aureus (MRSA), E. coli, K. pneumoniae, A. baumannii and P. aeruginosa) using
ciprofloxacin as a positive control and against two fungal strains (C. albicans and C. neoformans) using fluconazole and amphotericin B as positive controls. Compounds 9, 13a and 13b showed high to moderate antifungal activities against candida albicans (MIC values = 4–32 μg/ml), with considerable safety profiles; where no cytotoxicity against human embryonic kidney or red blood cells were detected at concentrations up to 32 μg/mL. Furthermore, compound 9 showed significant inhibitory activity against lansterol 14α-demethylase (IC50 = 0.27 μM), compared to the reference drug fluconazole (IC50 = 0.25 μM). Molecular docking of compound 9 into the active site of the cytochrome P450 enzyme revealed comparable binding modes and docking scores to those of fluconazole. Finally, in silico ADME studies prediction and drug-like properties of these compounds revealed
favorable oral bioavailability results.

Antibiotic resistance is one of the most important challenges of the 21st century. However, the growing
understanding of bacterial pathogenesis and cell-to-cell communication has revealed many potential
strategies for the discovery of drugs that can be used for the treatment of bacterial infections. Interfering
with bacterial virulence and/or quorum sensing could be a particularly interesting approach, because it is
believed to exert less selective pressure on the bacterial resistance than with traditional strategies,
geared toward killing bacteria or preventing their growth. Here, we discuss the mechanism of bacterial
virulence, presenting promising strategies and recently synthesized heterocyclic compounds to combat
future bacterial infections.

A novel series of benzimidazole derivatives wherein 4-(methylsulfonyl) phenyl pharmacophore attached via
its C-2 position was designed and synthesized. These compounds were evaluated in vitro as cyclooxygenase-1(COX-1)/cyclooxygenese-2(COX-2) inhibitors. Furthermore, the synthesized compounds were also in vivo evaluated for their anti-inflammatory activity and ulcerogenic liability. Examination of histopathological lesions was also performed to evaluate the cariogenic effect of most active compounds. In silico prediction of physicochemical properties, ADME, and drug-likeness profiles were also studied. Several compounds as 11b, 11k, 12b, and 12d showed selective inhibition to (COX-2) isozyme. Compound 11b showed the most potent (COX-2) inhibitory activity with (IC50 ¼ 0.10 mM) and selectivity index (SI ¼ 134); the tested compounds also have shown good anti-inflammatory activity. Regarding the ulcerogenic liability, compound 11b was also safest one (Ulcer Index) (UI ¼ 0.83). The results of the molecular docking studies is closely related to the results of the in vitro COX-2 inhibitory activities.

The chromatographic and lipophilicity characters of seven cephalosporins of different four classes (ce
phradine, cefaclor, cefprozil, cefixime, cefotaxime, ceftazidime and cefepime) were examined by salting out thin-layer chromatography (SOTLC). SOTLC using ammonium sulfate salt was employed to predict the
pophilicity of the proposed drugs via their retention behavior. The calculated RM0 values showed liner relationship with the molar concentration of ammonium sulfate in mobile phase in the range of 0.5–2.5 mol/L. Additionally, quantitative structure retention relationship (QSRR) was generated to figure out the relationship between the calculated chromatographic parameters (RM0 and C0) and log P of the studied cephalosporins. Good correlations were found between the chromatographically obtained retention meters (RM0 and C0) and some molecular descriptors of the examined drugs. Furthermore, an efficient QSAR model was carried out using the calculated chromatographic parameters (RM0 and C0) and log P of the studied cephalosporins to predict minimum inhibitory concentration (MIC) and blood brain barrier (BBB) penetration of the examined drugs. The study was extended to separate and quantify the selected biotics in their pure forms and pharmaceutical formulations. Normal phase thin layer chromatographic (NP-TLC) method using a usable developing system of acetone: methanol: water: ammonium hydroxide: glacial acetic acid (90: 10: 18: 3: 2, by volume) was successfully applied to resolve the studied porins. Linearity was achieved in the range of 0.2–3 μg/mL for most of the studied antibiotics. The oped SOTLC method can be considered as a good start alternative to reversed phase thin layer chromatography (RP-TLC) for prediction of the lipophilic properties of examined cephalosporins. Moreover, the proposed NP-TLC densitometric method can be easily applied for quality control analysis of the chosen drugs and other structurally related components.