Browsing by Author "Perera, I. C."

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Naphthalene appended diethylenetriamine based ligands and their platinum complexes as cancer theranostic agents
(Faculty of Science, University of Kelaniya Sri Lanka, 2024) Edirisinghe, L. G.; Perera, I. C.; Perera, N. T.
Dual action compounds with both diagnostic and therapeutic properties are extremely beneficial in treating cancers. Naphthalene sulfonamides are known fluorescent species due to the conjugated aromatic systems and they show sigma receptor targeting potential when bonded to diethylenetriamine. Here we present two new naphthalene sulfonamide ligands N(SO2-1-naphthalene) dien (L1) and N(SO2- 2-naphthalene)dien (L2) with their platinum complexes [Pt(N(SO2-1-naphthalene)dien)Cl]Cl (C1) and [Pt(N(SO2-2-naphthalene)dien)Cl]Cl (C2). The ligands L1 and L2 were synthesized by derivatizing the central N atom of diethylenetriamine, unlike the conventional ligands reported by derivatizing the terminal N atom of diethylenetriamine. All the compounds were synthesized in good yields and characterized using spectroscopic methods; UV-Visible, FTIR and 1H NMR spectroscopy. UV-Visible spectra of all compounds show absorption peaks due to n→π* electronic transitions in the region of 225-235 nm and absorption peaks corresponding to π→π* transitions were observed within the region of 265-300 nm. FTIR spectra aided to identify special functional group vibrations such as S-N bond vibrations and 1H NMR spectra were used in elucidating the structures of synthesized ligands and complexes. All of these species bear highly conjugated fluorophores (1-naphthalene and 2-naphthalene) which empower them as potential fluorescent imaging agents in diagnosis of cancer. By using Swiss TargetPrediction server, the biological targets for these two ligands were identified and sigma opioid receptor (SIGMAR-1) showed the highest probability showing their potential to act as cancer therapeutic drug leads. Moreover, both ligands obey the Lipinski rules ensuring their drug likeness. The structures of the ligands were geometrically optimized using the Gaussian 16 programme package, B3LYP/6-31G(d) level of theory. Theoretical molecular docking studies were performed to calculate binding affinities of ligands to the protein SIGMAR-1 (PDB ID: 5HK2) by AutoDock Vina wizard in PyRx 0.9.4 software, resulting -6.4 kcal/mol and -5.5 kcal/mol binding affinities for L1 and L2, respectively. Equipped with both therapeutic and diagnostic properties these compounds may serve as potential theranostic agents in the battle against cancer.
Rhenium tricarbonyl complexes as potential anticancer agents: a versatile approach for novel drug discovery and development
(Faculty of Science, University of Kelaniya Sri Lanka, 2024) Yasarathna, K. W. G. K. P.; Perera, I. C.; Perera, N. T.
Diethylenetriamine can serve as a bidentate as well as a tridentate ligand in coordination chemistry. Here we have synthesized asymmetric tridentate N donor ligands derived from diethylenetriamine with the aromatic groups; chlorobenzene and iodobenzene linked to a terminal nitrogen through a sulfonamide linkage. Two novel sulfonamide ligands; N(SO2chlorobenzene) dienH (L1) and N(SO2iodobenzene)dienH (L2) and their net neutral Re(I) tricarbonyl complexes; [Re(CO)3(N(SO2chlorobenzene)dien)] (C1) and [Re(CO)3(N(SO2iodobenzene)dien)] (C2) were synthesized. They were characterized using spectroscopic methods including 1H NMR, fluorescence, UV-Visible and FT-IR. ‘SwissTargetPrediction’ and ‘SwissADME’ servers were used for biological target predictions. Molegro Virtual Docker 2013.6.0.1 software was used to conduct the molecular docking study. Furthermore, BSA binding experiment was performed with UV-visible spectroscopic titrations. In UV-visible spectra, high energy absorption bands between 200 nm – 300 nm indicate the intraligand ᴫ-ᴫ* and n-ᴫ* transitions. High fluorescence intensities were observed for the ligands in the visible range while quenched fluorescence intensities were observed for their corresponding Re complexes. This lowered fluorescence may be due to the quenching of fluorescence upon coordinating of the ligand with the metal ion. The S-N stretching vibration appeared in free ligands; L1 and L2 have shifted towards higher frequencies in corresponding Re complexes; C1 and C2. 1H NMR spectra recorded in DMSO-d6 confirm that, upon complexation with the metal Re, the sulfonamide nitrogen deprotonates and two protons of the terminal nitrogen of the complexes orient toward (endo-NH) and away (exo-NH) from the CO ligands. The two ligands fulfill the requirements of Lipinski’s rule of 5 and exhibit an excellent bioavailability score of 0.55. Moreover, both ligands are predicted to bind with sigma receptors, an important drug target in the development of anticancer agents. L1, L2 and C1 showed MolDock scores of -94.83, -91.93 and -121.21, respectively for sigma receptors. In the BSA binding study, the calculated binding constant, Kb values for L1, L2, C1 and C2 are 7.44 x 104 M-1, 22.79 x 104 M-1, 54.27 x 104 M-1 and 2.62 x 104 M-1, respectively and are within the accepted range of Kb for drug-carrier complexes. The promising outcomes of in silico analysis and BSA binding study of these sulfonamide ligands and Re(I) complexes reveal that these compounds have the potential to be developed as anticancer drug leads and serum albumin could act as a good carrier to transport these compounds in vivo.