Jegathalaprathaban Rajesh

DNA interaction, antimicrobial, antioxidant and anticancer studies on Cu(II) complexes of Luotonin A

Luotonin A (L), a novel natural cytotoxic and anti-inflammatory alkaloid, chelated with copper(II) to improve its cytotoxic effect against the cancer cells. The complexes [Cu(L)H2OCl]Cl (1) and [Cu(L)2]Cl2 (2) are prepared by using copper(II) chloride and L with ligand/metal molar ratio of 1:1 and 2:1 respectively. A solution of complexes 1 &2 are characterized by physical spectroscopic methods using Ultraviolet-visible (UV-Vis) spectrophotometer, Fourier Transform-Infra red (FT-IR) spectroscopy, Electron Para magnetic Resonance Spectroscopy (EPR) and by electrochemical methods. The interaction of these complexes 1 &2 with calf thymus (CT-DNA) have been investigated by physical methods to propose the modes of DNA binding with the complexes 1 &2. Absorption spectral titration studies of complex 1 with CT-DNA shows a red-shift of 5nm with the DNA binding affinity of Kb, 8.65×103M-1, but complex 2does not show any red-shift with binding constant Kb, 7.32×103M-1 reveals that the complex 1 binding with DNA strongly than complex 2 and the binding occurs in between the base pairs of DNA as intercalation. Strong interactions of the two complexes 1 & 2 with CT-DNA have also been confirmed by fluorescence spectral titration studies. The evaluated values of KSV and Kass shows that, the complexes 1 &2 interact with DNA through the intercalation, coincide with other partial intercalators strongly than the free ligand L. Complex 1 exhibits potent antioxidant activity with SC50 value of 23.9±0.69μM is evaluated by DPPH radical scavenging assay and which has potent antimicrobial activity against pathogens than 2 and L. The anticancer activity of L, complexes 1 &2 against human breast cancer cell line (MCF-7) and cervical cancer cell line (HeLa) has also been studied by using fluorescence staining method. The IC50 values of L, complexes 1&2 against MCF-7 and HeLa cell lines with the incubation time intervals of 24hrs are 1 (5.0±0.25, 12.0±0.30μM)<2 (6.5±0.27, 15.0±0.30μM)<L (7.0±0.15, 25.0±0.35μM) respectively. Interestingly, complex 1 exhibits anticancer activity more potent than L against both MCF-7 and HeLa cell lines. The result of anticancer activity studies show that the cytotoxic activity of L against MCF-7 and HeLa cells is increased, when chelated with Cu(II).

Natural alkaloid Luotonin A and its affixed acceptor molecules: Serum albumin binding studies

Effective interaction of natural alkaloid Luotonin A (L) and its affixed acceptor molecules 1 and 2 with donor molecule as Bovine serum albumin (BSA) at various pH (4.0, 7.4 and 10.0) medium have been demonstrated using various conventional spectroscopic techniques. These analyses provide some valuable features on the interaction between BSA and acceptor molecules (L, 1 and 2). From the absorption and fluorescence spectral titration studies, the formation of ground-state complexes between the acceptor molecules (L, 1 and 2) and the BSA have been confirmed. The results of the afore titrations analysis reveal that, the strong binding of receptor 1 with BSA (Kapp 5.68×104M-1; KSV 1.86×106Lmol-1; Ka 6.42×105Lmol-1; Kass 8.09×106M-1; ΔG -33.35kJ/mol) at physiological pH medium (7.4) than other receptor molecules 2 and L. The Förster resonance energy transfer (FRET) efficiency between the tryptophan (Trp) residues of BSA and acceptor molecules L, 1 and 2 during the interaction, are 28.85, 85.24 and 53.25 % respectively. The superior binding efficacy of acceptor 1 at physiological pH condition has been further confirmed by FT-IR and Raman spectral analysis methods. Moreover, theoretical docking studies of acceptors L, 1 and 2 towards HSA have been demonstrated to differentiate their binding behaviours. It reveals that, acceptor 1 has the strongest binding ability with HSA through two hydrogen bonding and the Atomic contact energy (ACE) value of -483.96kcal/mol.

New pyrimidine based ligand capped gold and platinum nano particles: Synthesis, characterization, antimicrobial, antioxidant, DNA interaction and in vitro anticancer activities

In this research work, we have synthesized new pyrimidine based Schiff base ligand, 2-((4,6-dimethoxypyrimidine-2-yl)methyleneenamino)-6-methoxyphenol (DPMM) capped gold (Au) and platinum (Pt) nanoparticles (NPs) by modified Brust-Schiffrin method. The characteristics of DPMM-Au NPs and DPMM-Pt NPs have been examined by UV-Visible, FTIR, SEM, TEM and powder XRD analysis. SEM analysis result shows that surface morphology of the DPMM-Au NPs and DPMM-Pt NPs are in granular and spherical shape, correspondingly. The size of the DPMM-Au NPs and DPMM-Pt NPs are approximately 38.14±4.5 and 58.64±3.0nm respectively, which confirmed by TEM analysis. The DPMM-Au NPs and DPMM-Pt NPs have potent antimicrobial against Escherichia coli, Klebsiella pneumonia, Pseudomonas fluorescens, Shigella sonnei, Staphylococcus aureus and Aspergillus niger, Candida albicans, Candida tropicalis, Mucor indicus, Rhizopus strains. The DPMM-Au NPs and DPMM-Pt NPs have good antioxidant activities than the free ligand (DPMM). The spectroscopic and viscometric measurement confirms the hydrophobic DNA binding abilities of the newly prepared DPMM capped metal NPs. Moreover, the in vitro anticancer activity of DPMM, DPMM-Au NPs and DPMM-Pt NPs against cancer (MCF-7, HeLa & HEp2) and normal (NHDF) cell lines have performed using MTT assay. These results reveals that, DPMM-Au NPs and DPMM-Pt NPs having significant cytotoxic activity against the cancer cell lines and least toxic effect on normal cell line as compared to standard drug cisplatin.

Magnetic iron oxide nanoparticles (MIONs) cross-linked natural polymer-based hybrid gel beads: Controlled nano anti-TB drug delivery application: CONTROLLED NANO ANTI-TB DRUG DELIVERY APPLICATION

The nanosized rifampicin (RIF) has been prepared to increase the solubility in aqueous solution, which leads to remarkable enhancement of its bioavailability and their convenient delivery system studied by newly produced nontoxic, biodegradable magnetic iron oxide nanoparticles (MIONs) cross-linked polyethylene glycol hybrid chitosan (mCS-PEG) gel beads. The functionalization of both nano RIF and mCS-PEG gel beads were studied using various spectroscopic and microscopic techniques. The size of prepared nano RIF was found to be 70.20 ± 3.50 nm. The mechanical stability and swelling ratio of the magnetic gel beads increased by the addition of PEG with a maximum swelling ratio of 38.67 ± 0.29 g/g. Interestingly, this magnetic gel bead has dual responsive assets in the nano drug delivery application (pH and the magnetic field). As we expected, magnetic gel beads show higher nano drug releasing efficacy at acidic medium (pH = 5.0) with maximum efficiency of 71.00 ± 0.87%. This efficacy may also be tuned by altering the external magnetic field and the weight percentage (wt%) of PEG. These results suggest that such a dual responsive magnetic gel beads can be used as a potential system in the nano drug delivery applications.

One pot synthesis of new poly(vinyl alcohol) blended natural polymer based magnetic hydrogel beads: Controlled natural anticancer alkaloid delivery system

Facile one-pot synthesis has been demonstrated for new biocompatible and dual responsive magnetic iron oxide nanoparticles cross-linked poly(vinyl alcohol) (PVA) blended natural polymer chitosan (CS) based hydrogel beads (mCS-PVA) as a controlled natural anticancer alkaloid Luotonin A (LuA) delivery system. The prepared magnetic hydrogel beads were characterized using powder X-ray diffraction measurement, Fourier transform-infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, and vibrating sample magnetometer. The magnetic hydrogel beads are exhibited significant water retention and follow the second order kinetic model in swelling study. The swelling ratio of the magnetic gel beads increased by the addition of PVA and showed a maximum swelling ratio of 40.83 ± 1.01 g/g and follows non-Fickian water transport mechanism. Stimuli responsive mCS and mCS-PVA hydrogel beads functionalized with LuA is demonstrated for controlled release at physiological pH and under magnetic field. The magnetic hydrogel beads show highest LuA releasing efficacy at acidic medium (pH = 5.0) with maximum efficiency of 73.33 ± 1.44%. This efficacy may also be tuned by altering the external magnetic field as well as the weight percentage (wt %) of polyethylene glycol. It is clearly that the newly produced magnetic hydrogel beads can be served as an effective intestinal LuA delivery system.

Synthesis, spectral characterization, DNA interaction, antioxidant, and antimicrobial studies of new water soluble metal(II) complexes of morpholine based ligand

A new series of metal(II) complexes 1–5 of the type [M(L)(AcO)2H2O], where L is a bidentate ligand, 2-(3-morpholinopropylimino)methylphenol and M is Mn(II) (1), Co(II) (2), Ni(II) (3), Cu(II) (4), and Zn(II) (5), have been isolated and characterized by physico-chemical and spectral methods. Spectroscopic data supported the square pyramidal geometry around the central metal ion in the complexes 1–5. Absorption spectra and viscometric data indicated that the complexes 1–5 interacted with calf thymus (CT) DNA via intercalative strategy. Cleavage activities of complexes 1–5 with CT DNA were analyzed by gelelectrophoretic method. The in vitro antioxidant activity of complexes 1–5 was tested using the DPPH assay. The complexes 1–5 have been tested for antimicrobial activity against some pathogenic bacterial and fungal species by the agar well diffusion method.

A Schiff base receptor as a fluorescence turn-on sensor for Ni2+ ions in living cells and logic gate application

A new receptor (R) with easily available “off–on–off” colorimetric and fluorescent responses was synthesized and characterized using 1H NMR, 13C NMR, and ESI-MS studies. It exhibited selective and sensitive detection towards Ni2+ ion without having any interference from other tested metal ions. The changes in the obtained photophysical properties are due to the chelation-enhanced fluorescence effect (CHEF) caused by the ligand-to-metal charge transfer (LMCT) that occur after the addition of Ni2+ to the receptor. Density functional theory (DFT) calculations have theoretically supported the changes in the examined absorption and fluorescence spectra. Moreover, the receptor could be successfully oriented with the molecular logic functions of OR, AND, NOR, and NOT gates. Furthermore, the receptor efficacy was studied by examining the changes in intracellular Ni2+ in the HeLa cells. The receptor has been explored for a possible application in the real sample analysis and a test kit for the detection of Ni2+.

Multispectroscopic and bioimaging approach for the interaction of rhodamine 6G capped gold nanoparticles with bovine serum albumin

Binding interaction of Bovine Serum Albumin (BSA) with newly prepared rhodamine 6G-capped gold nanoparticles (Rh6G-Au NPs) under physiological conditions (pH 7.2) was investigated by a wide range of photophysical techniques. Rh6G-Au NPs caused the static quenching of the intrinsic fluorescence of BSA that resulted from the formation of ground-state complex between BSA and Rh6G-Au NPs. The binding constant from fluorescence quenching method (Ka = 1.04 × 104 L mol-1; LoD = 14.0 μM) is in accordance with apparent association constant (Kapp = 1.14 × 101 M-1), which is obtained from absorption spectral studies. Förster resonance energy transfer (FRET) efficiency between the tryptophan (Trp) residue of BSA and fluorophore of Rh6G-Au NPs during the interaction was calculated to be 90%. The free energy change (ΔG = -23.07 kJ/mol) of BSA-Rh6G-Au NPs complex was calculated based on modified Stern-Volmer Plot. The time-resolved fluorescence analysis confirmed that quenching of BSA follows static mechanism through the formation of ground state complex. Furthermore, synchronous and three-dimensional fluorescence measurement, Raman spectral analysis and Circular Dichroism spectrum results corroborate the strong binding between Rh6G-Au NPs and BSA, which causes the conformational changes on BSA molecule. In addition, fluorescence imaging experiments of BSA in living human breast cancer (HeLa) cells was successfully demonstrated, which articulated the value of Rh6G-Au NPs practical applications in biological systems.

A theranostic nanocomposite system based on iron oxide-drug nanocages for targeted magnetic field responsive chemotherapy

In this work, a theranostic nanocage system was developed for the targeted delivery of the anti-cancer agents camptothecin (CPT) and luotonin A (LuA). The core of the nanocage system (Fe3O4@OA-AD-SP NCs) was formed by biogenically synthesized Fe3O4 nanoparticles (NPs) decorated with a model anti-cancer drug (AD) and biosurfactant saponin (SP). The Fe3O4@OA-AD-SP NCs showed a high lipophilic AD loading efficiency (>80%) and a controlled pH-responsive drug release in stimulated cancerous cells in pH 6.4 media buffer. In addition, Fe3O4@OA-AD-SP NCs exhibited better serum protein binding efficacy at physiological pH values (7.4), furthering the important role of SP surface decoration. Particularly, these NCs showed better chemotherapeutic efficacy when examined in MCF-7 and HeLa cancer cell lines with a specific targeting capacity. Therefore, this study provides a new nano platform based on magnetic targeting and pH responsive lipophilic anticancer drug delivery to the cancer site.

Crystal structure, optical properties, DFT analysis of new morpholine based Schiff base ligands and their copper(II) complexes: DNA, protein docking analyses, antibacterial study and anticancer evaluation

New morpholine derived Schiff base ligands (HL1 and HL2) and their Cu(II) complexes [Cu(L1)2] (1) and [Cu(L2)2] (2) have been synthesized and characterized by 1H NMR, IR, UV-Vis, EPR studies and cyclic voltammetric analyses. Single crystal X-ray crystallography studies confirm the structure of newly synthesized Schiff base ligands HL1and HL2. The ground state electronic structures of Cu(II) complexes 1 and 2 have been investigated by DFT/B3LYP theoretical analysis with 6-31G (d,p) and LANL2DZ basis set. The affinity towards DNA and protein molecules have been evaluated using computational docking analysis and complex 2 expose significant binding ability with DNA as well as protein due to its towering hydrophobicity. Consequently, complex 2 reveals superior antibacterial activity against some bacterial species besides anticancer activity on human breast cancer (MCF-7) cells than complex 1 and Schiff base ligands (HL1 and HL2). These preliminary investigations strongly recommended that complex 2 can be used as a better antibacterial plus anticancer agent.