Design, synthesis and in silico prediction of drug-likeness properties of new ortho, meta and para- (2-cyano-3-(3,5-di-tert-butyl-4hydroxyphenyl)acrylamido)benzoic acids

Objective: The objective of the present study is to develop simple, rapid, sensitive, accurate and economic stability-indicating ultra-performance liquid chromatographic (UPLC) method for the simultaneous quantification of phenylephrine hydrochloride, chlorpheniramine maleate, paracetamol, guaiphenesin and bromhexine hydrochloride in bulk and tablet dosage form. Methods: The separation of drugs in the chromatographic column was accomplished on Hibar C18 (100 mm x 2.1 mm, 1.6 µm) column at a detection wavelength of 220 nm. The mobile phase was a combination of sodium phosphate monobasic monohydrate buffer (pH was adjusted to 3.5 with orthophosphoric acid) and acetonitrile in the ratio of 70:30 % v/v which was pumped at a flow rate of 0.3 ml/min. The column temperature was maintained at 30 °C and the injection volume was 0.3 µl. Forced degradation studies of drugs were carried out using acid, base, peroxide, light and heat. Results: All the five drugs have been eluted within 3 min. The retention times were found to be 0.834 min, 1.199 min, 1.600 min, 1.979 min and 2.525 min for phenylephrine, chlorpheniramine maleate, paracetamol, guaiphenesin and bromhexine respectively. The correlation coefficient (r2) was found to be 0.999 for all the drugs. The recovery levels were found to be in the range of 99.17 % to 100.69 %. RSD values of drugs were found to be below 2 %. The results of limit of detection and quantitation specified the sensitivity of the developed method. Significant degradation of drugs as a result of stress studies was found in acid, base and peroxide, but they were slightly degraded in photolytic and thermal conditions. The method has effectively resolved the degraded products. All the validation parameters were found to be within the limits according to International Conference on Harmonization (ICH) guidelines. Conclusion: A simple and rapid UPLC method was established for the determination of five drugs. Hence, the proposed method can be employed for the quality control of specified drugs in bulk and pharmaceutical formulation even in the presence of degradation products.

Succinic acid and its derivatives have many important uses, especially in pharmaceutical and polymer industry. The 2-(substituted benzylidene)succinic acids also known as substituted phenylitaconic acids are utilized in the synthesis of some lignans, lignanamides and renin inhibitors.  In view of this, the present in-silico study aimed to calculate the molecular properties, bioactivity score and toxicity of several benzylidenesuccinic acids as well as some selected anti-inflammatory drugs by computational methods.  The study revealed that all the compounds obeyed Lipinski’s rule of five, indicating drug likeness properties. The bioactivity data revealed that the 2-(substituted benzylidene)succinic acids were active as Nuclear receptor ligands, Enzyme inhibitors, GPCR ligands and Ion channel modulators. Among all, 2-(3,5-di-tert-butyl-4-hydroxybenzylidene)succinic acid was predicted as non-toxic with better in-silico molecular properties and bioactivity as Nuclear receptor ligand, Enzyme inhibitor, GPCR ligand, Ion channel modulator and Protease inhibitor compared to some of the predicted anti-inflammatory drugs.

Objective: To develop and validate a reverse phase high performance liquid chromatographic method for simultaneous estimation of ciprofloxacin and fluocinolone acetonide in bulk and pharmaceutical dosage form. Methods: The chromatographic separation was achieved on reverse phase Discovery Inertsil ODS3V Column, C18 (250 mm, 4.6 mm, 5 µm). The separation was achieved by employing the mobile phase consists of phosphate buffer (pH 4) and acetonitrile (40:60). The flow rate was 1.0 ml/min, at a detection wavelength of 295 nm. The proposed method was validated as per the International Council for Harmonisation (ICH) guidelines.Results: The retention time for ciprofloxacin and fluocinolone acetonide was found at 3.627 min and 5.037 min respectively. The proposed method was validated for specificity, accuracy, precision, linearity, the limit of detection (LOD), limit of quantitation (LOQ) and robustness. All validation parameters were within the acceptable range. The assay method was linear and found in the range from 12.5–37.25 µg/ml for ciprofloxacin and 0.625–1.875 µg/ml of fluocinolone acetonide. The relative standard deviation (RSD) values for ciprofloxacin and fluocinolone acetonide were 0.25 % and 0.18 %, respectively. Conclusion: A rapid, accurate and precise RP-HPLC method was developed for the simultaneous estimation of ciprofloxacin and fluocinolone acetonide in bulk and ointment formulation. The developed method was validated for specificity, accuracy, precision, linearity, the limit of detection, limit of quantitation and robustness according to ICH guidelines.

Grinding technique as a method employing green chemistry was selected for the synthesis of Schiff bases from 5-aminosalicylic acid and substituted benzaldehydes. Two known and eight novel 5-aminosalicylic acid Schiff bases were synthesized and recrystallized using methanol. All the compounds were characterized by their physical data and spectral studies such as IR, 1 H NMR, 13 C NMR and Mass. The synthesized compounds were evaluated for in vitro antioxidant activity by scavenging 1,1-diphenyl-2picrylhydrazyl (DPPH) and nitric oxide free radicals at 100μM concentration. The activity data revealed that the compounds with 4-hydroxy-3,5-dimethoxy substitution and 3,4-methylenedioxy substitution on N-benzylidene ring showed highest antioxidant activity in DPPH and nitric oxide scavenging models respectively. The activity of these compounds was found to be greater than 5-aminosalicylic acid and the standards employed. All the compounds were evaluated for antibacterial activity by agar well diffusion method using gram negative and gram positive bacteria such as E. coli, P. aeruginosa, S. aureus and B. subtilis. The results indicate that the evaluated compounds showed good to moderate antibacterial activity.