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Precipitation and cloud radar reflectivity at millimeter wave based on Mie’s scattering formula
In the past few decades, bioinorganic complexes of platinum have been a fascinating area of research in medicinal chemistry after the
discovery of anticancer activity of Cisplatin and the other next generation drugs like carboplatin and oxaliplatin. However, various
side-effects curtailed their wider applications in chemotherapy [1]. Hence, more focus has been paid towards the development of new
Pt(II) complexes with improved pharmacological effect and lower toxicity.
In the present study, our aim was to synthesise Pt(II) complexes [Pt(MAMP)Cl2], C1; [Pt(MAMP)(H2O)2](NO3)2, C2;
[Pt(MAMP)(GS)], C3; [Pt(MAMP)(TG)], C4; [Pt(MAMP)(cbdc)], C5 and [Pt(MAMP)(ox)], C6 having a fixed carrier ligand 2-
[(Methylamino)methyl]pyridine (MAMP) and variable leaving groups like Cl−, H2O, glutathionate (GS), thioglycolate (TG),
cyclobutanedicarboxylate (cbdc) and oxalate (ox) respectively [2]. All the complexes have been characterised through different
available spectroscopic and spectrometric techniques. MAMP has been selected as the carrier ligand owing to the fact that it is σ donor
and π acceptor in nature which can form strong bonds with Pt(II) and will not be substituted by any other species present inside the
cell. Most importantly MAMP is a π electron rich moiety which will assist its Pt(II) complexes to undergo intercalation or grove
binding with DNA and reduce its toxicity [3]. DNA binding ability of the aforementioned complexes has been investigated with Calf
thymus DNA (CT-DNA) through absorption, emission and viscosity titration as well as gel electrophoresis. Bovine serum albumin
(BSA) binding property has been explored through fluorometric titration. Different binding parameters for their interaction with DNA
as well as BSA have been evaluated. DNA as well as protein (BSA) binding experiments have shown all the studied complexes C1–
C6 bind strongly with CT-DNA and BSA which is also reflected from their different binding constant values (Kb, KSV, Kapp, KF) and
the number of binding sites per nucleophile (n). All of the complexes interact with DNA in a different manner in comparison to
cisplatin, carboplatin and oxaliplatin. Cytotoxicity of all the studied complexes are investigated on three different cancer cell lines
A549, MCF7, MDA-MB-231 as well as normal cell line i.e., rat skeletal muscle cells (L6 myotubes) and human embryonic kidney
cells (HEK 293) through MTT assay. All the complexes have shown comparable anticancer activity with cisplatin, carboplatin and
oxaliplatin. On the other hand, these complexes display less cytotoxicity on normal cell lines L6 myotubes and HEK 293 in
comparison to the above mentioned anticancer drugs. Results of ROS generation and degree of lipid peroxidation (LPO) study
indicate that all the studied complexes are almost devoid of toxicity which makes them most interesting. Study of cell cycle arrest by
the complexes on A549 has also been performed through flow cytometry where the complexes are found to arrest the cell cycle at S
and G2/M phase as concentration dependent manner. Finally, in order to understand the underlying mechanism of cancer cell death,
degree of apoptosis has been studied through immunoblot and immunofluorescence to measure the activated capase 3 by the studied
complexes. These findings indicate a remarkable apoptotic induction in A549 cells treated with the Pt(II) complexes. The complexes
under study have good prospect to be the anticancer drugs after further investigation of physiological processing and pharmacological
effects on living systems.
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