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Title:	Bis-indolylmethanes : synthesis, characterisation, biological evaluation and electrochemical pb(II) ion sensor development
Authors:	Nadrahtul Huda Misral (P93155)
Supervisor:	Siti Aishah Hasbullah, Assoc. Prof. Dr.
Keywords:	Bis-indolylmethanes Universiti Kebangsaan Malaysia -- Dissertations Dissertations, Academic -- Malaysia
Issue Date:	4-Sep-2021
Description:	Owing to the great molecular structure of indole that generally associated with various interesting applications in both biology and chemistry field, has led to a number of indole derivatives being synthesised and explored. Consequently, the primary aim of this project is to design and produce bis-indolylmethanes endowed with different substituents in order to evaluate their biological activities and sensor capability in identifying Pb(II) ion. As an integral part in achieving this aim, 26 bis-indolylmethane derivatives (19 �� 44) were synthesised using a convenient one pot reaction involving condensation of two main scaffolds (indole and benzaldehyde) and were characterised using spectroscopy techniques (FT-IR, NMR and MS). Bis-indolylmethanes 19 �� 31 were selected for in vitro CCK-8 assay in order to evaluate their antiproliferative activity against HL-60 cell. Our finding suggests that all synthesised bisindolylmethanes 19 �� 31, moderately inhibited the proliferation of HL-60 cell at a concentration of 50 μM except for ligands 23 and 31 which having a higher activity with IC50 values of 21.26 and 41.06 μM respectively. These two ligands were then selected for an additional biological and computational study to verify their antiproliferative potential. Both ligands 23 and 31 demonstrated the best potency of inhibition activity at a final concentration of 100 μM. Molecular docking study displayed that bis-indolylmethanes 23 and 31 stably binds into the anti-apoptotic protein (Bcl-2) binding hot spot (P2) via p-p interaction formed with Phe101 amino acid. In addition, UV-vis titration with ctDNA indicated the antiproliferative properties of bisindolylmethanes which have been ascribed to its capability in binding to DNA and leading to cancer cell death with the binding constant value (Kb) for ligands 23 and 31 are 6.02×104 M��1 and 1.04×104 M��1 respectively. It was also found that both ligands showed a non-carcinogenic behaviour upon analysation using a toxicity DNA biosensor. On the other hand, synthesised bis-indolylmethanes 32 �� 44 were optimised using density functional theory (DFT) to study their HOMO-LUMO energy together with molecular electrostatic potential (MEP), and ligand 37 was finalised for the sensor development. A new, simple to use and cost effective sensor for selective determination of Pb(II) ion was reported. The electrochemical sensor was developed by physical immobilisation of bis-indolylmethane 37 with SBA-15 deposited on a carbon screen printed electrode (CSPE). Characterisations of ligand 37 immobilised into the SBA-15 hexagonal pores were carried out by FESEM and XRD analysis. The immobilised bisindolylmethane derivative on SBA-15 matrix showed an electrocatalytic ability for the oxidation of Pb(II) ion at ��0.52 V versus Ag/AgCl reference electrode which resulted to direct determination of Pb(II) ion using differential pulse voltammetry (DPV) analysis. The voltammetric sensor based on bis-indolylmethane derivative exhibited a dynamic linear response range towards Pb(II) ion over the concentration range of 1×10��5 M to 4×10��3 M (R2 = 0.9963) with a good limit of detection (LOD) at 6.8×10��6 M. The electrochemical sensor produced a stable potential reading above 80% of its initial response for up to seven days of storage duration, with a response time of 30 min. The developed sensor was successfully applied to the real sample of Allium tuberosum (chive leaves), which were in good agreement with the ones analysed by ICP-OES standard method, with recovery percentage of 90.4% and 97.6% for two concentrations of Pb(II) ion evaluated (n=3). Collectively, the bis-indolylmethanes produced in this study can be classified as potential anticancer agents and metal ion ionophores which could contribute in both medicinal and food safety field.,Tesis ini tidak ada ��Perakuan Tesis Sarjana / Doktor Falsafah��,Ph.D
Pages:	209
Publisher:	UKM, Bangi
Appears in Collections:	Faculty of Science and Technology / Fakulti Sains dan Teknologi

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