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Two new copper clusters, {Cu4} and {Cu4Cd6}, with polydentate aminoalcohol ligands, diethanol propanolamine (H3L1) and bis–tris{2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol} (H6L2), have been synthesized under mild conditions and characterized thoroughly by single-crystal X-ray diffraction (XRD), infrared spectroscopy, elemental analysis, powder XRD, magnetic and DFT studies, and absorption and fluorescence spectroscopy. The cluster {Cu4} exhibits a rare tetranuclear copper cubane core whereas {Cu4Cd6} forms an unusual heterometallic cage owing to the introduction of the second metal Cd into the ligand. A hexapodal ligand (H6L2) with N and O donor atoms was chosen deliberately for the construction of a high-nuclearity cluster, i.e., {Cu4Cd6}. Interestingly, both the clusters displayed significant cytotoxicity towards human cervical (HeLa) and lung (A549) cancer cells as evident from the shallow IC50 values [15.6 ± 0.8 μM (HeLa), 18.5 ± 1.9 μM (A549) for {Cu4}, and 11.1 ± 1.5 μM (HeLa), 10.2 ± 1.3 μM (A549) for {Cu4Cd6}] obtained after a 24 h incubation. However, moderate toxicity was observed toward immortalized lung epithelial normal cells (HPL1D) with IC50 values of 32.4 ± 1.2 μM for {Cu4} and 27.6 ± 1.7 μM for {Cu4Cd6}. A cellular apoptotic study using HeLa cells revealed that the {Cu4} cluster triggered apoptosis at both the early and late phases while the {Cu4Cd6} cluster facilitate apoptosis mainly at the late apoptotic stage. A standard 2′,7′-dichlorodihydrofluorescein-diacetate (DCFH-DA) test affirms that both the clusters enhanced ROS production inside the cancer cells, responsible for promoting cell apoptosis. The decanuclear {Cu4Cd6} clusters demonstrated better anticancer activity compared to the tetranuclear {Cu4} clusters, indicating the role of high nuclearity and additional Cd metal in the enhanced intracellular production of ROS. [ABSTRACT FROM AUTHOR]

Nickel(II) complexes [Ni(cur)(L) 2 (OAc) (1-3) where L is N,N-donor heterocyclic bases namely 1,10-phenanthroline (phen in 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq in 2), dipyrido[3,2-a:2′,3′-c]phenazine (dppz in 3) and Hcur is curcumin were prepared, fully characterized and light-induced in vitro anticancer activity studied. Three nickel(II) complexes containing acetylacetonato (Hacac) ligand, viz. [Ni(acac)(L) 2 (OAc) (4-6) where L is phen (in 4), dpq (in 5), dppz (in 6) were prepared and used as controls. Complex 4 was structurally characterized by single crystal X-ray diffraction technique, which revealed an octahedral NiN 4 O 2 geometry around the metal centre. Complexes 1 - 3 showed an intense curcumin-based band at ∼440 nm in DMSO-Tris-HCl buffer (pH = 7.2) (1:4 v/v) which masks the nickel based d-d band. The curcumin comlexes (1 - 3) were redox inactive at the nickel centre, whereas the acetylacetonato complexes (4 - 6) displayed an irreversible voltammetric response at ∼1.00 V vs. Ag/AgCl reference electrode in DMF. The complexes bind to calf thymus DNA (ct -DNA) with considerable affinity and interacted with human serum albumin (HSA) with moderate affinity. The Ni(II) curcumin complexes display significant in vitro light-induced cytotoxicity in HeLa (human cervical carcinoma) and A549 (lung cancer cells) involving reactive oxygen species (ROS), with very low dark toxicity. The complexes were found to be much less toxic to immortalized lung epithelial normal cells (HPL1D). Confocal microscopic images using complex 2 and 3 showed that they primarily localize in the cytosol of A549 cells. The mechanism of cell death is mainly apoptosis in nature showing arrest of sub-G1 phase of cell cycle progression in A549 cells under visible light exposure and involves significant loss of mitochondrial membrane potential as observed from JC-1 assay. Synopsis: Curcumin in its complexed form to Ni(II) along with phenanthroline bases show significant binding propensity towards calf thymus DNA and human serum albumin along with excellent photo-enhanced cytotoxicity in HeLa and A549 cancer cells with very low dark toxicity. Image 1 • The curcumin complexes display significant light-induced cytotoxicity in cancer cells. • The complexes primarily localize in the cytosol of A549 cells. • The mechanism of cell death is mainly apoptosis in nature in A549 cells. [ABSTRACT FROM AUTHOR]

Oxo-bridged dimeric Fe(III) complexes having tetradentate salen-type Schiff-base ligands show pH dependent reversible binding to human serum albumin and significant in vitro photoinduced cytotoxicity in cancer cells in low energy visible light primarily via ROS mediated apoptosis. • Oxo-bridged dimeric Fe(III) complexes show excellent photocytotoxicity in HeLa, MCF-7 and MDA-MB-231 cells. • The complexes generate ROS on excitation with low energy visible light. • They induce cell death via apoptosis mechanism. Four oxo-bridged dimeric Fe(III) complexes, viz. [(µ - O){Fe(L)} 2 (1 – 4), where L is N,Ń-bis(naphtalidene)-ethylenediamine, (H 2 L1 in 1); N,Ń - bis(naphtalidene)-1,2-phenylenediamine, (H 2 L2 in 2); N,Ń-bis(naphtalidene)-4-nitro-1,2-phenylenediamine (H 2 L3 in 3) and N,Ń-bis(naphtalidene)-4-carboxyl-1,2-phenylenediamine, (H 2 L4 in 4) were synthesized for their potential application as photochemotherapeutic agents in low energy visible light. The solid-state structure of complex 2 was confirmed by X-ray crystallography. The complexes bind to human serum albumin (HSA) reversibly in a pH dependent manner, which could be a potential carrier of the molecules in blood plasma. They also bind to calf-thymus (ct) DNA with considerable affinity. In vitro cellular experiments show that the complexes display significant photo-enhanced cytotoxicity in human cervical cancer (HeLa) and human breast cancer (MCF-7 and MDA-MB-231) cells with low dark toxicity. ICP-MS analysis show that the complexes enter HeLa cells in a dose-dependent manner. Flow cytometric and confocal microscopic experiments demonstrate that the complexes kill cancer cells on exposure to visible light primarily via apoptosis through the generation of reactive oxygen species (ROS). [ABSTRACT FROM AUTHOR]

In this work, we report a novel dinuclear Sn (II) complex, [Sn2(Hpdm)2(H2O)6] 2H2O 2Cl (1) (H2pdm = pyridine‐2,6‐dimethanol), which has been crystallized out and characterized by elemental analysis, FTIR, 1H and 13C NMR, single crystal X‐ray studies and Density Functional Theory (DFT) analysis. X‐ray structure of 1 has confirmed it to be a dinuclear alkoxo‐bridged Sn (II) species where each metal adopts a seven coordinate distorted pentagonal bipyramidal (pbp) geometry. This is the first hepta‐coordinated Sn (II) complex ever isolated apart from already reported stannylenes. Spin density plots from DFT support the +2 oxidation state of each tin metal. Hirshfeld surface analysis reveals the presence of various H‐bonding interactions in the molecule and molecular docking results along with DFT confirm higher binding affinity of the present complex towards DNA. Moreover, the complex exhibits promising anticancer activities against HeLa and A549 cancer cell lines. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is multifactorial, progressive neurodegeneration with impaired behavioural and cognitive functions. The multitarget-directed ligand (MTDL) strategies are promising paradigm in drug development, potentially leading to new possible therapy options for complex AD. Herein, a series of novel MTDLs phenylsulfonyl-pyrimidine carboxylate (BS-1 to BS-24) derivatives were designed and synthesized for AD treatment. All the synthesized compounds were validated by 1HNMR, 13CNMR, HRMS, and BS-19 were structurally validated by X-Ray single diffraction analysis. To evaluate the plausible binding affinity of designed compounds, molecular docking study was performed, and the result revealed their significant interaction with active sites of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The synthesized compounds displayed moderate to excellent in vitro enzyme inhibitory activity against AChE and BuChE at nanomolar (nM) concentration. Among 24 compounds (BS-1 to BS-24), the optimal compounds (BS-10 and BS-22) displayed potential inhibition against AChE; IC 50 = 47.33 ± 0.02 nM and 51.36 ± 0.04 nM and moderate inhibition against BuChE; IC 50 = 159.43 ± 0.72 nM and 153.3 ± 0.74 nM respectively. In the enzyme kinetics study, the compound BS-10 displayed non-competitive inhibition of AChE with Ki = 8 nM. Respective compounds BS-10 and BS-22 inhibited AChE-induced Aβ 1-42 aggregation in thioflavin T-assay at 10 μM and 20 μM, but BS-10 at 10 μM and 20 μM concentrations are found more potent than BS-22. In addition, the aggregation properties were determined by the dynamic light scattering (DLS) and was found that BS-10 and BS-22 could significantly inhibit self-induced as well as AChE-induced Aβ 1-42 aggregation. The effect of compounds (BS-10 and BS-22) on the viability of MC65 neuroblastoma cells and their capability to cross the blood-brain barrier (BBB) in PAMPA-BBB were further studied. Further, in silico approach was applied to analyze physicochemical and pharmacokinetics properties of the designed compounds via the SwissADME and PreADMET server. Hence, the novel phenylsulfonyl-pyrimidine carboxylate derivatives can act as promising leads in the development of AChE inhibitors and Aβ disaggregator for the treatment of AD. [Display omitted] • A series of 24 phenylsulfonyl-pyrimidine carboxylate derivatives were designed and synthesized. • All compounds showed moderate to excellent in vitro inhibitory activity against AChE and BuChE at nanomolar concentration. • Two compounds BS-10 and BS-22 exhibited promising AChE inhibition. • Highlighted compounds BS-10 and BS-22 significantly inhibited Aβ aggregation. • BS-10 and BS-22 displayed high potential for BBB permeability. • BS-10 and BS-22 exhibited significant neuroprotection towards MC65 cells while no neurotoxicity. [ABSTRACT FROM AUTHOR]