Background: Hetero atom containing compounds are well studied class of organic compounds exhibits variety of properties and applications. Design and synthesis of new heterocyclic compounds are always of great interest in synthetic and medicinal organic chemistry. Benzothiazole or 2-aminobenzothiazole scaffold based derivatives were reported to display a wide range of biological activities including anticancer, anti-tubercular, antiviral, fungicidal, etc. On the other hand, 1,3,4-oxadiazoles were permit to increase their biological activities due to H-bonding with receptors. These derivatives possess diverse biological activities which include anticancer, antiviral, antifungal, antibacterial and antidepressant etc. Due to interesting biological activity information of about these hetero cyclic moieties, benzothiazole/2-aminobenzothiazole and 1,3,4-oxadiazoles moieties, we chose to design a new series of heterocyclic compounds by mimicking these two types of scaffolds in a single molecule for our study. Methods: The 1,3,4-oxadiazole linked benzothiazole derivatives were synthesized by condensation of, 2-(4-(5-(benzo[d]thiazol-2-yl)-1,3,4-thiadiazol-2-yl)-2,6-dimethoxyphenoxy)acetohydrazide and POCl3 under reflux conditions. All these ten compounds structures were confirmed by spectral data 1H & 13C NMR, Mass, CHN analysis etc. Further, these compounds were evaluated for their anticancer activity against four human cancer cell lines, A549, MCF7, A375 and HT-29 in comparison to CA4 as a reference drug. We also carried out docking studies of these compounds in the Colchicines binding site of Tubulin (PDB_ID: 1SA0) using Glide docking tool indicated that the ligands show good interactions with active site residues. Results: A new series of 1,3,4-oxadiazole fused benzothiazole derivatives were synthesized successfully in totally six steps starting with 4-hydroxy-3,5-dimethoxybenzoyl chloride. All these newly synthesized compounds structures were confirmed by spectral studies and elemental analysis. As we designed for anticancer activity, they were assessed for their anticancer activity against four human cancer cell lines in comparison to a reference drug CA4. As expected, all the ten compounds exhibited anticancer activities against four cancer cell lines with half maximal inhibitory concentration (IC50) values ranging from 0.01 µM to 12.3 µM. The docking studies indicated all the compounds exhibited good binding energies with the receptor. Conclusion: In this study we designed a new series heterocyclic compounds by mimicking two types of scaffolds benzothiazole/2-aminobenzothiazole and 1,3,4-oxadiazoles moieties in a single molecule based on their biological activity in the literature. They were synthesized successfully and molecular structures were confirmed by spectral studies. As expected, all the compounds exhibited anticancer activities against four cancer cell lines. This study can provide a roadmap for design and synthesis of new drug molecules for antitumor and anticancer activity.

Herein, we report the design, synthesis and biological evaluation of the anti-inflammatory activities of N-phenyl sulfonamide linked N-acylhydrazones (NPS–NAH), using the molecular hybridization approach. Hybrid compounds were further validated by theoretical studies. Compound 1f from series-1 and compound 2a from series-2 exhibited strong selective COX-2 enzyme inhibition at IC₅₀ = 8.9 μM and 8.4 μM respectively. Effective in vivo anti-inflammatory profiling of potent and selective COX-2 inhibitors, including compound 1f and 2a was carried out and compared with known COX-2 inhibitors. Subsequently, these compounds were tested for antioxidant activity, and 1h (IC₅₀ = 28.62 μM) from series-1 and compound 2d (IC₅₀ = 25.34 μM) from series-2 were found to be potent anti-oxidants. Additionally, these compounds were screened for antibacterial activity, and compound 1l and 2b exhibited better Gram +ve and −ve anti-bacterial activity than the reference standards, Ciprofloxacin and Norfloxacin. These results validated the idea of exploiting the hybridization strategy for the identification of new N-phenyl sulfonamide–NAH derivatives for optimizing anti-inflammatory, antioxidant and anti-bacterial activities.

The present work describes a novel stability-indicating method development and validation for separation and identification of degradation products, known and genotoxic impurities in recently FDA approved (Ibrutinib) an anti-cancer drug using RP-HPLC/PDA and QDa mass detectors. Separation of all impurities could be achieved using stationary phase column (X-Select CSH, C18, 150 mm × 4.6 mm × 3.5 μm) with a flow rate of 1 ml/minute and total run time 85 minutes. Degradation was carried out; Ibrutinib was sensitive to acid, base and peroxide conditions. In the base degradation sample, a major degradation impurity was found, which was identified their mass value and structure information using QDa mass detector. Ibrutinib was found to be stable under heat, UV, humidity and water conditions. No interference was found at identified impurities, degradation products and ibrutinib peak retention time. The proposed method was validated as per ICH Q2 (R1) guidelines. It was observed that the percentage recovery was found to be 95 % to 105 % and linearity over the range of LOQ level, 50 %, 100 % 150 % and 300 % level of concentrations with R²: 0.999 to 1.000. According to validation and degradation results, the method was found to be good stability indicating nature as well as user-friendly.