Indian Association for the Cultivation of Science

In this study, we report the synthesis of 4'-O-methoxyethyl deoxyuridine and 4'-O-methoxyethyl deoxycytidine phosphoramidites and their incorporation into oligonucleotides. The 3'-exonuclease experiment indicated a significant increase in stability with the incorporation of 4'-O-MOE dU alone (T_1/2 = 178 min) and in combination with phosphorothioate modification (T_1/2 = 13 h) in dT₁₀-mer. Western blot studies demonstrated that 4'-O-MOE-dU and 4'-O-MOE-dC modifications were well-tolerated when placed at both overhang regions and multiple positions within the passenger strand of anti-Bcl2 siRNAs. Moreover, overhang-modified siRNA duplexes showed no significant change in the IFNα level compared to native siRNA. Molecular modelling studies revealed that the 4'-O-MOE group makes multiple steric interactions with 3'-exonuclease residues, contributing to improved nuclease resistance. Additionally, this modification accommodates well within the PAZ domain, potentially influencing RNAi activity. Overall, the modified deoxynucleotides could enhance the stability and efficacy of nucleic acid drugs.

The use of metallodrugs in cancer therapy received widespread interest after the successful application of cisplatin and its analogous compounds as chemotherapeutic medications. Despite the development of various metallodrugs in past years, platinum-based chemotherapeutic agents are the only clinically approved metallodrugs that primarily interact with genomic DNA and trigger severe dose-limiting adverse side effects in cancer patients. As a consequence, the advancement of new risk-free metallodrugs has become a topmost concern in cancer research to minimize toxicity and improve therapeutic outcomes. G-quadruplex (G4) DNA structures have recently come to light as an attractive drug target in cancer therapy because of their gene regulation ability and role in maintaining genomic stability. Their presence in telomere and promoter region of oncogenes has the potential to induce apoptosis in cancer cells through the inhibition of telomerase activity and gene expression. Therefore, the development of new G4 DNA targeting small molecular entities including metal complexes came out as a viable approach for uprooting cancer disease. Beyond organic small molecules, innumerable metal complexes have been developed in past years to target G4 DNA structures in the context of cancer therapy. This review primarily aims to highlight these metal complexes through a comprehensive discussion about their structural properties, their binding interactions with G4 DNA, their cancer cell growth inhibition mechanisms, and their efficacy in both cellular and in vivo systems, to decode their potential as anti-cancer drugs. Additionally, the potential of these metal complexes in the field of bio-imaging and photodynamic therapy is also explored.

In supramolecular chemistry, thiourea binding sites have gained paramount attention due to their ability to bind anions employing directional hydrogen bonding (HB) interactions. In this work, we report a new thiourea-based anion receptor, BDTU, incorporating electron-deficient benzothiadiazole (BTD) as a signaling unit. The binding affinity and signaling ability of BDTU toward various anions of different geometry and basicity are investigated by ¹H NMR, UV-vis, and fluorescence techniques in CH₃CN. As determined by NMR spectroscopic analyses, BDTU shows moderate selectivity toward chloride (Cl^-) over other halides and oxyanions, forming relatively stable 1:2 host-guest stoichiometric complex that is stabilized by thiourea NH HBs. In this regard, the single crystal X-ray structure of the Cl^- complex of BDTU has revealed short and directional intermolecular N─H⋯Cl^- HB with chloride. Importantly, this strong HB with Cl^- is successfully utilized in the solid-liquid extraction of chloride. Furthermore, the photophysical studies reveal a reversible anion sensing behavior of BDTU toward fluoride (F^-) in CH₃CN. Thus, BDTU is demonstrated for dual applications in extraction as well as sensing of anions.