Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of molecules which have been found to be active against cancer cells with chemopreventive properties by targeting cyclooxygenase (COX-1 and COX-2) and lipoxygenase (LOX), commonly upregulated (particularly COX-2) in malignant tumors. Arene ruthenium(ii) complexes with a pseudo-octahedral coordination environment containing different ancillary ligands have shown remarkable activity against primary and metastatic tumors as reported earlier. This work describes the synthesis of four novel ruthenium(ii)-arene complexes viz. [Ru(η-p-cymene)(nap)Cl] 1 [Hnap = naproxen or (S)-2-(6-methoxy-2-naphthyl)propionic acid], [Ru(η-p-cymene)(diclo)Cl] 2 [Hdiclo = diclofenac or 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, [Ru(η-p-cymene)(ibu)Cl] 3 [Hibu = ibuprofen or 2-(4-isobutylphenyl)propanoic acid] and [Ru(η-p-cymene)(asp)Cl] 4 [Hasp = aspirin or 2-acetoxy benzoic acid] using different NSAIDs as chelating ligands. Complexes 1-3 have shown promising antiproliferative activity against three different cell lines with GI (concentration of drug causing 50% inhibition of cell growth) values comparable to adriamycin. At the concentration of 50 μM, complex 3 is more effective in the inhibition of cyclooxygenase and lipooxygenase enzymes, followed by complex 2 and complex 1 in comparison to their respective free NSAID ligands indicating a possible correlation between the inhibition of COX and/or LOX and anticancer properties. Molecular docking studies with COX-2 reveal that complexes 1 and 2 having naproxen and diclofenac ligands exhibit stronger interactions with COX-2 than their respective free NSAIDs and these results are in good agreement with their relative experimentally observed COX inhibition as well as anti-proliferative activities.
Finding the most effective method for cancer treatment
is one of
the thought-provoking tasks. Drug delivery by collapsing of metallogel
to the cancer cell is an appealing way out. Cancer cells have an acidic
environment due to excessive accumulation of lactic acid. In this
work, the novel G5 gelator with a strategically free
carboxylic acid arm has been designed and fabricated and characterized
by several spectroscopic and microscopic techniques. These experiments
suggest the formation of an ordered supramolecular gel with clover-leaf-like
morphology. Mechanical properties from rheological measurements suggest
the viscoelastic nature of the gel. Furthermore, we have obtained
crystals of G5 from the pure dimethyl sulfoxide solution,
whereas gelation gets induced by addition of water. This G5 gelator loses its gelation capability once the carboxylate is esterified
by layering with methanol, which furnished the crystals of Me-G5′ (G5′ = G5-H). Further, the G5 gelator is used
for the formation of ruthenium metallogel. Interestingly, we obtained
the monomeric species [Ru(G5′)(η6-p-cymene)Cl] [Ru(II)G5] only in confined gel
space upon addition of a [Ru2(η6-p-cymene)2Cl4] dimer to G5. The Ru(II)G5 metallogel has an inherent anticancer
property with an IC50 value of 10.53 μM for the A549
cancer cell line. Treatment of the Ru(II)G5 metallogel
by lactic acid for mimicking the acidic environment of the malignant
cell results in collapsing of the gel by releasing the ruthenium metal
ion. This released ruthenium ion binds with the lactic acid derivative
making the gelator G5 free and producing a new compound Ru(II)L, which has also shown the anticancer property. The
molecular docking study revealed that the released G5 could interact with a monocarboxylate transporter to disrupt the
lactate transport chain, which might induce apoptosis.
Three new classes of ionic organoselenium
compounds containing
cationic benzimidazolium and imidazolium ring systems with selenocyanates
as counterions are described. The cyclization of N,N′-disubstituted
benzimidazolium and imidazolium bromides having N-(CH2)2-Br and N-(CH2)3-Br groups in the presence of potassium selenocyanate
(KSeCN) led to formation of the corresponding selenazolium selenocyanates
(21a, 21b, 22a, and 22b) and selenazinium selenocyanates (21c, 21d, 22c, and 22d). However, the open-chain
selenocyanates with additional selenocyanate counterions (21e, 21f, 22e, and 22f) were
formed from the N,N′-disubstituted benzimidazolium and imidazolium
bromides having N-(CH2)6-Br
groups. Mechanistic studies were carried out to understand the feasibility
of such cyclization processes in the presence of KSeCN. The compounds
were studied further for their potencies to catalytically reduce H2O2 in the presence of thiols. Interestingly, the
cyclic selenazolium (21a, 21b, 22a, and 22b) and selenazinium compounds (21c, 21d, 22c, and 22d) exhibited
significantly higher antioxidant activities than the corresponding
acyclic selenocyanates (21f, 22e, and 22f). Selected compounds (22d and 22e) were further evaluated for their potencies in modulating the intracellular
level of reactive oxygen species (ROS) in a representative macrophage
cell line (RAW 264.7). Owing to the cationic nature of compounds,
they may target and scavenge mitochondrial ROS in the cellular medium.
The synthesis of benzylic and mesitylenic organochalcogenocyanates has been described and the compounds have been studied for their anti-proliferative activities in breast cancer cells (MDA-MB-231, MCF-7 and T-47D).
The biothiol-reactive organotrisulfide-based fluorogenic donors of H2S are designed for the monitoring of intracellular and lysosomal delivery of H2S with a concomitant turn-on fluorescence.
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