Benzimidazole based Pt(<scp>ii</scp>) complexes with better normal cell viability than cisplatin: synthesis, substitution behavior, cytotoxicity, DNA binding and DFT study

Mitra, Ishani; Mukherjee, Subhajit; Reddy, P B Venkata; Dasgupta, Subrata; K, Jagadeesh C. Bose; Mukherjee, Sandip; Linert, Wolfgang; Moi, Sankar Ch.

doi:10.1039/c6ra17788c

Cited by 78 publications

(55 citation statements)

References 60 publications

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“…According to the Scatchard equation, [41] a plot of r / C f versus r gave K b values of (0.12±0.05)×10 5 and (3.11±0.09)×10 5 M −1 from the fluorescence data for the CQPQ‐gold(I) hybrid and CQDP respectively, showing a possible displacement of EB similar to other metal complexes with reported biological activity [42–44] . This displacement can indicate intercalation or minor groove interaction [45–48] . The results also show that the DNA‐binding affinity of CQPQ‐gold(I) hybrid is mild, which agrees with the results obtained from electronic absorption spectra and viscosity measurements.…”

Section: Resultsmentioning

confidence: 57%

A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent

et al. 2020

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Plasmodium parasites kill 435 000 people around the world every year due to unavailable vaccines, a limited arsenal of antimalarial drugs, delayed treatment, and the reduced clinical effectiveness of current practices caused by drug resistance. Therefore, there is an urgent need to discover and develop new antiplasmodial candidates. In this work, we present a novel strategy to develop a multitarget metallic hybrid antimalarial agent with possible dual efficacy in both sexual and asexual erythrocytic stages. A hybrid of antimalarial drugs (chloroquine and primaquine) linked by gold(I) was synthesized and characterized by spectroscopic and analytical techniques. The CQPQ‐gold(I) hybrid molecule affects essential parasite targets, it inhibits β‐hematin formation and interacts moderately with the DNA minor groove. Its interaction with PfTrxR was also examined in computational modeling studies. The CQPQ‐gold(I) hybrid displayed an excellent in vitro antimalarial activity against the blood‐stage of Plasmodium falciparum and liver‐stage of Plasmodium berghei and efficacy in vivo against P. berghei, thereby demonstrating its multiple‐stage antiplasmodial activity. This metallic hybrid is a promising chemotherapeutic agent that could act in the treatment, prevention, and transmission of malaria.

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Section: Resultsmentioning

confidence: 57%

A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent

et al. 2020

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“…To calibrate the pH tutor, a standard phosphate buffer solution (KH 2 PO 4 /Na 2 HPO 4 ) was used. The pharmacokinetic measurements and absorption titrations of DNA and BSA were performed with a Shimadzu UV 1800 spectrophotometer . To control the temperature for each experiment, a thermoelectric cell temperature controller (Model TCC-100, accuracy ±0.1 °C) was attached with the UV spectrophotometer.…”

Section: Methodsmentioning

confidence: 99%

Development of Anticancer Activity of the Pt(II) Complex with N-Heterocyclic Amine: Its In Vitro Pharmacokinetics with Thiol and Thio-Ethers, DNA and BSA Binding, and Cell Cycle Arrest

Pan

Mitra

Mukherjee

et al. 2021

ACS Appl. Bio Mater.

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A dichloro Pt(II) complex with N-heterocyclic amine cis-Pt(PIEAM)Cl2, C-1 (where PIEAM = 1-(2-aminoethyl)piperidine) was synthesized and hydrolyzed to the corresponding [Pt(PIEAM)(OH2)2]2+ C-2 to explore its bioactivity and cytotoxic property. Biorelevant sulfur-containing small tripeptide glutathione (GSH)- and amino acid dl-methionine (dl-meth)-substituted complexes [Pt(PIEAM)(GSH)] C-3 and [Pt(PIEAM)(dl-meth)]+2 C-4 were synthesized and characterized. In vitro pharmacokinetic reactions of complex C-2 → C-3 and C-4 with GSH and dl-meth, respectively, were studied under pseudo-first-order reaction conditions. The high and negative entropy of activation (ΔS ⧧) and low and positive enthalpy of activation (ΔH ⧧) values were deduced from the Eyring equation to propose an associative mechanism. To find out the biotransformation of complex C-1, C-2, and Pt(II)–S chelates C-3 and C-4 to Pt(II)-DNA adducts, DNA binding affinity of C-1–C-4 was examined by UV–visible spectroscopy, fluorescence quenching, and gel electrophoresis methods. BSA binding activity of these complexes was emphasized for their biological importance and the “drug reservoir” activity. Anticancer activity of these complexes on HEp 2 (laryngeal), MDA-MB-231 (breast), and A549 (lung) cancer cell lines was found to be remarkable as compared to the recognized anticancer drugs such as cisplatin, carboplatin, and oxaliplatin. Cell cycle arrest was also explored on HEp 2 cells of the complexes at a concentration corresponding to IC50 value and displayed significant cell death at the sub-G1 phase.

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“…The cytotoxicity of the essential oil of S. cumini leaves was evaluated against human liver cancer cells (HepG2) using MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay [28,48,49]. The cell lines were obtained from American Type Culture Collection.…”

Section: Assessment Of Cytotoxic Activitymentioning

confidence: 99%

GC/MS Analysis of Essential Oil and Enzyme Inhibitory Activities of Syzygium cumini (Pamposia) Grown in Egypt: Chemical Characterization and Molecular Docking Studies

et al. 2021

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Syzygium cumini (Pomposia) is a well-known aromatic plant belonging to the family Myrtaceae, and has been reported for its various traditional and pharmacological potentials, such as its antioxidant, antimicrobial, anti-inflammatory, and antidiarrheal properties. The chemical composition of the leaf essential oil via gas chromatography–mass spectrometry (GC/MS) analysis revealed the identification of fifty-three compounds representing about 91.22% of the total oil. The identified oil was predominated by α-pinene (21.09%), followed by β-(E)-ocimene (11.80%), D-limonene (8.08%), β-pinene (7.33%), and α-terpineol (5.38%). The tested oil revealed a moderate cytotoxic effect against human liver cancer cells (HepG2) with an IC50 value of 38.15 ± 2.09 µg/mL. In addition, it effectively inhibited acetylcholinesterase with an IC50 value of 32.9 ± 2.1 µg/mL. Furthermore, it showed inhibitory properties against α-amylase and α-glucosidase with IC50 values of 57.80 ± 3.30 and 274.03 ± 12.37 µg/mL, respectively. The molecular docking studies revealed that (E)-β-caryophyllene, one of the major compounds, achieved the best docking scores of −6.75, −5.61, and −7.75 for acetylcholinesterase, α-amylase, and α-glucosidase, respectively. Thus, it is concluded that S. cumini oil should be considered as a food supplement for the elderly to enhance memory performance and for diabetic patients to control blood glucose.

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Benzimidazole based Pt(ii) complexes with better normal cell viability than cisplatin: synthesis, substitution behavior, cytotoxicity, DNA binding and DFT study

Abstract: Water soluble Pt(ii) complexes with higher viability towards normal cells and comparable cytotoxicity to cancer cells as compared to cisplatin.

Cited by 78 publications

References 60 publications

A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent

A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent

Development of Anticancer Activity of the Pt(II) Complex with N-Heterocyclic Amine: Its In Vitro Pharmacokinetics with Thiol and Thio-Ethers, DNA and BSA Binding, and Cell Cycle Arrest

GC/MS Analysis of Essential Oil and Enzyme Inhibitory Activities of Syzygium cumini (Pamposia) Grown in Egypt: Chemical Characterization and Molecular Docking Studies

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