Two bisoprolol derivatives, N-acetyl bisoprolol and N-formyl bisoprolol, belonging to the beta-blocker class of antihypertensive drugs, were synthesized using acetylation and formylation reactions. The yields of the reactions were determined to be 32.40% for N-acetyl bisoprolol and 20.20% for N-formyl bisoprolol. In silico methods such as molecular docking, molecular dynamics simulation and SwissADME prediction were employed to evaluate the potential of these bisoprolol derivatives as antihypertensive drugs. These methods were used to assess the interaction between the bisoprolol derivatives and various receptors associated with hypertension, including human angiotensin I-converting enzyme (PDB ID: 1O8A), renin (PDB ID: 2V0Z), beta-1 adrenergic receptors (PDB ID: 4BVN, 7BVQ), voltage-dependent L-type calcium channel subunit alpha-1S (PDB ID: 6JP5) and mineralocorticoid receptor (PDB ID: 6L88). Our results demonstrated the highest binding energy when bisoprolol and its derivatives bound to 4BVN, with binding energy values of 6.74 kcal mol-1, 7.03 kcal mol-1 and 7.63 kcal mol-1 for bisoprolol, N-acetyl bisoprolol and N-formyl bisoprolol, respectively. The stability of these complexes was confirmed by molecular dynamics simulations, with a root-mean-square deviation value of approximately 2. Furthermore, the SwissADME results indicated that both derivatives exhibited similar properties to the reference drug bisoprolol.

Aspirin and omeprazole combining has proven their effectiveness clinically in the treatment and prevention of cardiovascular diseases in patient with gastric diseases and gastric ulcers. Simultaneous determination of omeprazole and aspirin in their combination is a challenge due to the overlapping spectra of these drugs. Six smart and different spectrophotometric methods were developed for the analysis of omeprazole and aspirin in binary mixture and pharmaceutical dosage form. These smart methods characterized by simplicity and accuracy. The first two methods based on minimal mathematical data processing based on the zero order absorption spectra were; dual wavelength and advanced absorbance subtraction methods. The third method is first and second derivative spectrophotometric method that based on derivative spectra. The last three methods based on ratio spectra manipulation are named; ratio difference, mean centering and derivative ratio spectrophotometric methods. The linearity range of omeprazole was 2-20 μg/mL for dual wavelength method and 2-30 μg/mL for the other ones, while aspirin showed a good linearity over a range of 2.5-30 μg/mL for all methods. The correlation coefficients were greater than 0.999. The results of the developed methods are statistically compared with each other and with the results of the reported HPLC method showing no significant difference. The greenness of the developed methods was assessed using eco-scale scoring method revealing excellent greenness of the applied methods. This spectrophotometric methods is more sensitive and greener with comparing by the reported one so, these developed methods are considered eco-friendly to the environment.