Cancer is one of the most common and lethal disease in the world, therefore, patients need new and potent anticancer agents for treatment. In this study, starting from vanillin, 24 new compounds, which are 12 thiosemicarbazone (4a‐h, 5i‐j, 6k) and 12 thiazolidin‐4‐one (7a‐h, 8i‐j and 9k) derivatives, were synthesized and characterized by Nuclear Magnetic Resonance (NMR), High‐Resolution Mass Spectroscopy (HRMS), and Fourier‐transform Infrared (FTIR) techniques. In vitro cytotoxic effects were investigated on CCD‐1079Sk human healthy fibroblast and MDA‐MB‐231 human breast cancer cell lines. For MDA‐MB‐231, molecules showed IC50 in ranging of 88.08 ± 0.027–16.54 ± 0.031 μM (Doxorubicin: 61.70 ± 0.021 μM) and for CCD‐1079Sk, molecules showed IC50 in ranging of 192.36 ± 0.018–13.58 ± 0.035 μM (Doxorubicin:52.01 ± 0.028 μM). Compounds 6k and 7f were found most selective and potent anticancer agents compared to Doxorubicin used as a standard drug.

Drug-conjugated nanoassemblies potentiate the efficiency of anticancer drugs through the advantages of high drug-loading capacity and passive/active targeting ability in cancer therapy. This study describes the synthesis of gemcitabine (Gem) and cisplatin (cisPt) dual-drug-functionalized glyco-nanoassemblies (GNs) for anticancer drug delivery systems. It also investigates the pH-triggered drug delivery of the conventional anticancer drug cisPt. A Gem-functionalized well-defined glycoblock copolymer backbone (P(iprFruMA-b-MAc)-Gem), which consists of fructose and methacrylic acid segments, was synthesized via a reversible addition–fragmentation chain transfer (RAFT) polymerization method. Following the hydrolysis of the protecting groups on the backbone copolymer, cisPt functionalization of P(FruMA-b-MAc)-Gem in aqueous media was carried out during the transformation of glycoblock polymers into self-assembled spherical glyco-nanoassemblies (GN3). Monodrug-functionalized glyco-nanoassemblies were also prepared either with Gem (GN1) or cisPt (GN2) to compare the synergetic effect of dual-drug conjugated glyco-nanoassemblies (GN3). The sizes of glyco-nanoassemblies GN1, GN2, and GN3 were found as 5.76 ± 0.64, 59.80 ± 0.13, and 53.80 ± 3.90 nm and dispersity (Đ) values as 0.476, 0.292, and 0.311 by dynamic light scattering (DLS) measurement, respectively. The in vitro studies revealed that the drug-free glyco-nanoassemblies are biocompatible at concentrations higher than 296 μg/mL. The drug-conjugated glyco-nanoassemblies (GN1 and GN2) exhibited in vitro cytotoxicity against human breast cancer cell lines of MDA-MB-231 comparable to free Gem and cisPt, illustrating an efficient drug release into the tumor environment. Additionally, GNs exhibited higher selectivity and preferential cellular internalization in MDA-MB-231 when compared to healthy cell lines of CCD-1079Sk. These dual-drug conjugated GNs can effectively enhance the killing of cancer cells and increase synergistic chemotherapy.

In this study, twenty new anthranilic acid hydrazones 6–9 (a–e) were synthesized and their structures were characterized by Fourier‐transform Infrared (FT‐IR), Nuclear Magnetic Resonance (1H‐NMR – 13C‐NMR), and High‐resolution Mass Spectroscopy (HR‐MS). The inhibitory effects of the compounds against COX‐II were evaluated. IC50 values of the compounds were found in the range of >200–0.32 μM and compounds 6e, 8d, 8e, 9b, 9c, and 9e were determined to be the most effective inhibitors. Cytotoxic effects of the most potent compounds were investigated against human hepatoblastoma (Hep‐G2) and human healthy embryonic kidney (Hek‐293) cell lines. Doxorubicin (IC50: 8.68±0.16 μM for Hep‐G2, 55.29±0.56 μM for Hek‐293) was used as standard. 8e is the most active compound, with low IC50 against Hep‐G2 (4.80±0.04 μM), high against Hek‐293 (159.30±3.12), and high selectivity (33.15). Finally, molecular docking and dynamics studies were performed to understand ligand‐protein interactions between the most potent compounds and COX II, Epidermal Growth Factor Receptor (EGFR), and Transforming Growth Factor beta II (TGF‐βII). The docking scores were calculated in the range of −10.609–−6.705 kcal/mol for COX‐II, −8.652–−7.743 kcal/mol for EGFR, and −10.708–−8.596 kcal/mol for TGF‐βII.