Design, synthesis, modelling studies and biological evaluation of 1,3,4-oxadiazole derivatives as potent anticancer agents targeting thymidine phosphorylase enzyme.

A series of novel 1,3,4-oxadiazole derivatives with substituted phenyl ring were designed and synthesized with an objective of discovering newer anti-cancer agents targeting thymidine phosphorylase enzyme (TP). The 1,3,4-oxadiazole derivatives were synthesized by simple and convenient methods in the lab. Chemical structure of the all the synthesized compounds were characterized by IR, 1H NMR and mass spectral methods and evaluated for cytotoxicity by MTT method against two breast cancer cell lines (MCF-7 and MDA-MB-231). Further, results of TP assay identified that 1,3,4-oxadiazole molecules displayed anti-cancer activity partially by inhibition of phosphorylation of thymidine. The TP assay identified SB8 and SB9 as potential inhibitors with anti-cancer activity against both the cell lines. The molecular docking studies recognized the orientation and binding interaction of molecule at the active site amino acid residues of TP (PDB: 1UOU). Acute toxicity studies of compound SB8 at the dose of 5000 mg/kg has identified no signs of clinical toxicity was observed. The SARs study of synthesized derivatives revealed that the substitution of phenyl ring with electron withdrawing group at ortho position showed significant TP inhibitory activity compared to para substitution. The experimental data suggests that 1,3,4-oxadiazole with substituted phenyl can be taken as a lead for the design of efficient TP inhibitors and active compounds which can be taken up for further studies.

Production, surface modification and biomedical applications of nanodiamonds: A sparkling tool for theranostics.

Diamond nano-particles or nanodiamonds (NDs) are nano-scale carbon allotropes and exhibit characteristic mechanical and optical properties. Unlike other nanocarbon materials NDs are highly bio-compatible and comparatively safe which makes them the material of future interest in the field of medicine. NDs are synthesized by various techniques which includes detonation technique, chemical vapour deposition, high pressure high temperature etc. and followed by post-synthesis processing such as purification, surface modification and functionalization. Interestingly, the versatile surface chemistry of NDs facilitates the conjugation with various functional groups and chemical moieties, which can be utilized for biomedical applications. Due to their unique optical and spectroscopic properties, NDs have been studied in bio-imaging in which NDs doped with specific atoms such as nitrogen, sodium, boron and were used for cell labelling and/or cell tracking. NDs have also been explored as a targeted drug delivery platform in conjugation with various therapeutic agents such as anti-cancer, anti-bacterial, anti-inflammatory agents etc., attributed to its flexible surface properties. Apart from this, macromolecules like protein and nucleic acids can be delivered in an efficient and safe manner with NDs. This review focuses on the synthesis, surface modification and various biomedical applications of nanodiamonds as a theranostic agent.