A new series of indoline-2-one derivatives was designed and synthesized based on the essential pharmacophoric features of VEGFR-2 inhibitors. Anti-proliferative activities were assessed for all derivatives against breast (MCF-7) and liver (HepG2) cancer cell lines, using sunitinib as a reference agent. The most potent anti-proliferative derivatives were evaluated for their VEGFR-2 inhibition activity. The effects of the most potent inhibitor, 17a, on cell cycle, apoptosis, and expression of apoptotic markers (caspase-3&-9, BAX, and Bcl-2) were studied. Molecular modeling studies, such as docking simulations, physicochemical properties prediction, and pharmacokinetic profiling were performed. The results revealed that derivatives 5b, 10e, 10g, 15a, and 17a exhibited potent anticancer activities with IC₅₀ values from 0.74–4.62 µM against MCF-7 cell line (sunitinib IC₅₀ = 4.77 µM) and from 1.13–8.81 µM against HepG2 cell line (sunitinib IC₅₀ = 2.23 µM). Furthermore, these compounds displayed potent VEGFR-2 inhibitory activities with IC₅₀ values of 0.160, 0.358, 0.087, 0.180, and 0.078 µM, respectively (sunitinib IC₅₀ = 0.139 µM). Cell cycle analysis demonstrated the ability of 17a to induce a cell cycle arrest of the HepG2 cells at the S phase and increase the total apoptosis by 3.5-fold. Moreover, 17a upregulated the expression levels of apoptotic markers caspase-3 and -9 by 6.9-fold and 3.7-fold, respectively. In addition, 17a increased the expression level of BAX by 2.7-fold while decreasing the expression level of Bcl-2 by 1.9-fold. The molecular docking simulations displayed enhanced binding interactions and similar placement as sunitinib inside the active pocket of VEGFR-2. The molecular modeling calculations showed that all the test compounds were in accordance with Lipinski and Veber rules for oral bioavailability and had promising drug-likeness behavior.

A series of novel 1,2,3-triazole-linked ciprofloxacin-chalcones 4a-j were synthesised as potential anticancer agents. Hybrids 4a-j exhibited remarkable anti-proliferative activity against colon cancer cells. Compounds 4a-j displayed IC₅₀s ranged from 2.53-8.67 µM, 8.67–62.47 µM, and 4.19–24.37 µM for HCT116, HT29, and Caco-2 cells; respectively, whereas the doxorubicin, showed IC₅₀ values of 1.22, 0.88, and 4.15 µM. Compounds 4a, 4b, 4e, 4i, and 4j were the most potent against HCT116 with IC₅₀ values of 3.57, 4.81, 4.32, 4.87, and 2.53 µM, respectively, compared to doxorubicin (IC₅₀ = 1.22 µM). Also, hybrids 4a, 4b, 4e, 4i, and 4j exhibited remarkable inhibitory activities against topoisomerase I, II, and tubulin polymerisation. They increased the protein expression level of γH2AX, indicating DNA damage, and arrested HCT116 in G2/M phase, possibly through the ATR/CHK1/Cdc25C pathway. Thus, the novel ciprofloxacin hybrids could be exploited as potential leads for further investigation as novel anticancer medicines to fight colorectal carcinoma.

Many studies have been carried out to find synthetic pathways to nicotinonitriles (3-cyanopyridines) and their analogs, which has resulted in a substantial amount of knowledge on their biological, therapeutic, and medical characteristics. Some of nicotinonitrile derivatives have emerged as marketed drugs such as bosutinib, milrinone, neratinib, and olprinone. In this review, we discuss the recently synthesized nicotinonitrile-based hybrids that possess important biological activity and will be useful for drug discovery and development.

Simvastatin (SV) is a lipid lowering drug exhibits anti-inflammatory and anabolic effects on the bone, so it could
be utilized for the local treatment of periodontitis. However, the poor solubility of SV limits its penetration
through the gingival sulcus. Encapsulating SV into microsponges may have the potential to enhance the dissolution and subsequently its local penetration. In this study, SV microsponges had been prepared using the
emulsion-solvent evaporation technique where, Eudragit RS-100 was employed as the polymer. The % encapsulation efficiency(%EE) of drug approached 77.32 ± 2.03. The prepared microsponges were free flowing,
spherical in shape having narrow size distribution range. The particle size of the prepared microsponges was
93.79 ± 7.21 μm in diameter with a small polydispersity index (PDI) of 0.0059 ± 0.0008. In-vitro dissolution
studies of SV microsponges showed that the solubility of SV had significantly enhanced upon inclusion inside the
microsponges. Fourier transform infrared (FT-IR) spectroscopy indicated hydrogen bond formation between SV
and Eudragit RS-100. The prepared microsponges were incorporated in chitosan 2% gels. A clinical study was
conducted on 24 selected patients having bony periodontal defects to compare the efficacy of chitosan 2% gel
containing free (SV) with that containing SV microsponge in treatment of chronic periodontitis. Results showed
that the chitosan gels containing SV microsponges exhibited significant reduction in both pocket depth and
clinical attachment loss compared to those prepared with free SV. This might be attributed to hydrogen bond
formation between microsponges entrapped SV and chitosan, thus microsponges are auspicious as a carrier for
SV for local treatment of periodontitis.