Water-Soluble Small Organic Fluorophores for Oncological Theragnostic Applications: Progress and Development.

Cancer is one of the major noncommunicable diseases, responsible for millions of deaths every year worldwide. Though various cancer detection and treatment modalities are available today, many deaths occur owing to its late-stage detection and metastatic nature. Noninvasive detection using luminescence-based imaging tools is considered one of the promising techniques owing to its low cost, high sensitivity, and brightness. Moreover, these tools are unique and valuable as they can detect even the slightest changes in the cellular microenvironment. To achieve this, a fluorescent probe with strong tumor uptake and high spatial and temporal resolution, especially with high water solubility, is highly demanded. Recently, several water-soluble molecules with emission windows in the visible (400-700 nm), first near-infrared (NIR-I, 700-1000 nm), and second near-infrared (NIR-II, 1000-1700 nm) windows have been reported in literature. This review highlights recently reported water-soluble small organic fluorophores/dyes with applications in cancer diagnosis and therapeutics. We systematically highlight and describe the key concepts, structural classes of fluorophores, strategies for imparting water solubility, and applications in cancer therapy and diagnosis, i.e., theragnostics. We discuss examples of water-soluble fluorescent probes based on coumarin, xanthene, boron-dipyrromethene (BODIPY), and cyanine cores. Some other emerging classes of dyes based on carbocyclic and heterocyclic cores are also discussed. Besides, emerging molecular engineering methods to obtain such fluorophores are discussed. Finally, the opportunities and challenges in this research area are also delineated.

Synthesis, Characterization, Cytotoxicity, Cellular Imaging, Molecular Docking, and ADMET Studies of Piperazine-Linked 1,8-Naphthalimide-Arylsulfonyl Derivatives.

To reduce the mortality and morbidity associated with cancer, new cancer theranostics are in high demand and are an emerging area of research. To achieve this goal, we report the synthesis and characterization of piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives (SA1-SA7). These compounds were synthesized in good yields following a two-step protocol and characterized using multiple analytical techniques. In vitro cytotoxicity and fluorescent cellular imaging of the compounds were assessed against non-cancerous fibroblast (3T3) and breast cancer (4T1) cell lines. Although the former study indicated the safe nature of the compounds (viability = 82-95% at 1 µg/mL), imaging studies revealed that the designed probes had good membrane permeability and could disperse in the whole cell cytoplasm. In silico studies, including molecular docking, molecular dynamics (MD) simulation, and ADME/Tox results, indicated that the compounds had the ability to target CAIX-expressing cancers. These findings suggest that piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives are potential candidates for cancer theranostics and a valuable backbone for future research.

Synthesis, Characterization, Antiglycation Evaluation, Molecular Docking, and ADMET Studies of 4-Thiazolidinone Derivatives.

The design and development of new small-molecule glycation inhibitors are essential for preventing various chronic diseases, including diabetes mellitus, immunoinflammation, cardiovascular, and neurodegenerative diseases. 4-Thiazolidinone or thiazolidine-4-one is a well-known heterocyclic compound with the potential to inhibit the formation of advanced glycation end products. In the present work, we report the synthesis and characterization of four new 5-arylidene 3-cyclopropyl-2-(phenylimino)thiazolidin-4-one (1-4) compounds and their human serum albumin glycation inhibitory activity. One of the compounds 5-(2H-1,3-benzodioxol-5-ylmethylidene)-3-cyclopropyl-2-(phenylimino)-1,3-thiazolidin-4-one (3) showed potent inhibition in the synthesis of initial, intermediary, and final products of glycation reactions. Besides, conformational changes in the α-helix and ß-sheet (due to hyperglycemia) were also found to be reversed upon the addition of (3). Experimental findings were complemented by computational [molecular docking, ADME/Tox, and density functional theory (DFT)] studies. The docking scores of the compounds were in order 1 > 3 > 2 > 4, indicating the importance of the polar group at the 5-arylidene moiety. The results of ADME/Tox and DFT calculations revealed the safe nature of the compounds with high drug-likeness and stability. Overall, we speculate that the results of this study could provide valuable insights into the biological activity of 4-thiazolidinones.

Synthesis, anticancer activity, molecular docking and molecular dynamics studies of some pyrazole-chalcone hybrids.

Four new hybrid compounds (H1-H4) bearing pyrazole (S1 and S2) and chalcone (P1 and P2) fragments were synthesized and characterized. Compounds were assayed for their ability to inhibit the proliferation of human lung (A549) and colon (Caco-2) cancer cell lines. Besides, toxicity against normal cells was determined using the human umbilical vein endothelial cells (HUVEC). In silico molecular docking, molecular dynamics (MD) simulation and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were carried out to predict the binding modes, protein stability, drug-likeness and toxicity of the reported compounds. The in vitro anticancer activity of the tested compounds revealed dose-dependent cell-specific cytotoxicity. In silico studies revealed that the compounds have a good binding affinity, possess appropriate drug-likeness properties and have low toxicity profiles.Communicated by Ramaswamy H. Sarma.

In silico evaluation of 4-thiazolidinone-based inhibitors against the receptor for advanced glycation end products (RAGE).

Non-enzymatic glycation of biomolecules by reducing sugars led to several products, including the advanced glycation end products (AGEs), the accumulation of which has been linked to various life-threatening diseases. The binding of AGEs to their respective protein receptors for advanced glycation end products (RAGE) can initiate a cascade of reactions, which may alter physiological conditions. The present work investigates the potential of 4-thiazolidinones as RAGE inhibitors. We performed an extensive computational study to identify the structural requirements needed to act as RAGE inhibitors. To achieve this goal, 4-thiazolidinone-based compounds available in PubChem, ZINC15, ChEMBL, and ChEBI databases were screened against RAGE (PDB: 4LP5), leading to the identification of top five drug-like candidates with a high binding affinity to RAGE V-domain catalytic region. Drug likeness, absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the top-scoring compounds have been studied and discussed. Global molecular descriptors, chemical reactivity, hardness, softness, etc., have been estimated. Finally, molecular dynamics (MD) simulations at 100 ns were carried out to check the stability and other properties. Overall, we believe that the identified compounds can potentially attenuate RAGE-AGE interactions.Communicated by Ramaswamy H. Sarma.

New Epoxy and Hardener System Based on an Imidazolium Ionic Liquid as an Anticorrosive Coating for Steel in the Marine Environment.

The large sizes of cations and anions of organic salts are the driving force for the application of ionic liquids (organic salts) in harsh salty conditions. Moreover, the formation of crosslinked ionic liquid networks as anti-rust and anticorrosion protective films on the substrate surfaces repels seawater salt and water vapor from their surface to prevent corrosion. In this respect, an imidazolium epoxy resin and polyamine hardener as ionic liquids were prepared by the condensation of either pentaethylenehexamine or ethanolamine with glyoxal and p-hydroxybenzaldehyde or formalin in acetic acid as a catalyst. The hydroxyl and phenol groups of the imidazolium ionic liquid were reacted with epichlorohydrine in the presence of NaOH as a catalyst to prepare polyfunctional epoxy resins. The chemical structure, nitrogen content, amine value, epoxy equivalent weight, thermal characteristics, and stability of the imidazolium epoxy resin and polyamine hardener were evaluated. Moreover, their curing and thermomechanical properties were investigated to confirm the formation of homogeneous, elastic, and thermally stable cured epoxy networks. The corrosion inhibition and salt spray resistance of the uncured and cured imidazolium epoxy resin and polyamine as coatings for steel in seawater were evaluated.

Chemical, biological and in silico assessment of date (P. dactylifera L.) fruits grown in Ha'il region.

Background: Dates palm (Phoenix dactylifera L.) fruits are among the most widely used fruits in the Middle East and African nations. Numerous researchers confirmed the presence of phytochemicals in P. dactylifera L. fruit and its by-products with broad-ranging biological activities. Objectives: In the present work, phytochemical and biological assessments of two different cultivars of date fruit (Shishi M1 and Majdool M2 grown in the Ha'il region of Saudi Arabia) have been carried out. Methods: Date fruits were extracted and analyzed by gas chromatography-mass spectrometry (GS-MS),liquid chromatography-mass spectrometry (LC-MS) and Fourier-transform infrared spectroscopy (FT-IR)techniques. The lyophilized methanolic extracts were analyzed for their in-vitro antiproliferative andcytotoxicity against colon cancer (HCT116) cell line. To identify the possible constituents responsible for the bioactivity, in-silico molecular docking and molecular dynamics (MD) simulation studies were carried out. Results: Both cultivars exhibited in-vitro anticancer activity (IC50 = 591.3 µg/mL and 449.9 µg/mL for M1 and M2, respectively) against colon cancer HCT-116 cells. The computational analysis results indicated procyanidin B2 and luteolin-7-O-rutinoside as the active constituents. Conclusion: Based on these results, we conclude that these cultivars could be a valuable source for developing health promoter phytochemicals, leading to the development of the Ha'il region, Saudi Arabia.

Non-covalent interactions (NCIs) in π-conjugated functional materials: advances and perspectives.

The design and development of functional materials with real-life applications are highly demanding. Understanding and controlling inter- and intra-molecular interactions provide opportunities to design new materials. A judicious manipulation of the molecular structure significantly alters such interactions and can boost selected properties and functions of the material. There is burgeoning evidence of the beneficial effects of non-covalent interactions (NCIs), showing that manipulating NCIs may generate functional materials with a wide variety of physical properties leading to applications in catalysis, drug delivery, crystal engineering, etc. This prompted us to review the implications of NCIs on the molecular packing, optical properties, and applications of functional π-conjugated materials. To this end, this tutorial review will cover different types of interactions (electrostatic, π-interactions, metallophilic, etc.) and their impact on π-conjugated materials. Attempts have also been made to delineate the effects of weak interactions on opto-electronic (O-E) applications.

Characterization and application of ligno-cellulosic fibers derived from Robinia Pseudoacacia for the bio-sorption of methylene blue from water.

Ligno-cellulosic biomasses had been recognized for their potential use to produce chemicals and biomaterials. The current study focused on the use of a new cellulosic Robinia Pseudoacacia fiber and extracted lignin as adsorbents for methylene blue (a cationic dye). The biomaterials were analyzed using FT-IR spectroscopy, SEM, XRD, and TGA-DTA techniques. The surface of Robinia fibers was rough and porous. The crystallinity index (CrI) value for Robinia fibers was found to be 32%. The ability of the studied samples to remove methylene blue from water was assessed under the variation of time, pH, dye concentration, temperature, and NaCl concentration. The maximum adsorption capacity of methylene blue reached 191 mg/g for Robinia fibers and it achieved 22 mg/g for the extracted lignin (T = 20 °C, pH = 6, and time = 90 min). The adsorption data complied with the pseudo second-order kinetic model and both Langmuir and Freundlich isotherms. Based on these findings, the process suggested the occurrence of many physicochemical interactions between methylene blue molecules and the studied biomaterials. The adsorption mechanism was exothermic, non-spontaneous, and it was described by the decrease of the disorder. Adsorption results proved that Robinia fiber was an attractive candidate for the removal of cationic dyes from water.

A low-cost and abundant Robinia Pseudoacacia fiber and its extracted lignin are characterized and further studied as adsorbents for cationic dyes under the change of the experimental conditions.

Synthesis of Mixed Arylalkyl Tertiary Phosphines via the Grignard Approach.

Trialkyl and triaryl phosphines are important classes of ligands in the field of catalysis and materials research. The wide usability of these low-valent phosphines has led to the design and development of new synthesis routes for a variety of phosphines. In the present work, we report the synthesis and characterization of some mixed arylalkyl tertiary phosphines via the Grignard approach. A new asymmetric phosphine is characterized extensively by multi-spectroscopic techniques. IR and UV-Vis spectra of some selected compounds are also compared and discussed. Density functional theory (DFT)-calculated results support the formation of the new compounds.

Synthesis and characterization of a new meso-tetrakis (2,4,6-trimethylphenyl) porphyrinto) zinc(II) supported sodium alginate gel beads for improved adsorption of methylene blue dye.

Chemical modification of a biopolymer offers a simple strategy to realize new materials with added benefits. In this paper, meso-tetrakis(2,4,6-trimethylphenyl) porphyrinto) zinc(II) supported sodium alginate gel beads were successfully prepared, characterized, and used for the removal of a cationic dye from aqueous solution. The chemical structure of the prepared composite beads was confirmed by FT-IR, SEM, XRD and TGA/DTG techniques. Analytical data suggested that the sodium alginate beads and meso-tetrakis(2,4,6-trimethylphenyl) porphyrinto) zinc(II) complex interacted via non-covalent interaction (H-bonding) mode. The morphological micrographs showed spherical and smooth composite beads. The crosslinking of hydroxyl and carboxylate groups of the biopolymer with calcium ions and the incorporation of meso-tetrakis(2,4,6-trimethylphenyl) porphyrinto) zinc(II) into alginate matrix resulted in a small decrease of residual mass. The maximum adsorption capacities of methylene blue, at 20 °C, were found to be 52.3 mg/g and 34.8 mg/g for sodium alginate composite beads (3%) and plain sodium alginate beads, respectively. The adsorption process followed Freundlich isotherm and pseudo second order kinetics. The thermodynamic study displayed an exothermic and non-spontaneous process.

Synthesis, characterization, anticancer and in silico studies of a pyrazole-tethered thiazolidine-2,4-dione derivative.

A new pyrazole-tethered thiazolidine-2,4-dione derivative (8) has been synthesized by the Knoevenagel condensation of 3-(4-nitrophenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (4) and 3-(2,4-dioxothiazolidin-3-yl)propanenitrile (7). The structure of the final compound was confirmed by standard spectroscopic techniques including IR spectroscopy, 1H-NMR spectroscopy, and ESI-MS mass spectrometry. Molecular features including frontier molecular orbital (HOMO-LUMO) energies, reactivity descriptors and molecular electrostatic potential (ESP) of the title molecule were determined using density functional theory (DFT) calculation. The in vitro cytotoxicity of both the intermediate (4) and final (8) compounds were investigated against cancerous (SW-480 and MCF-7) and normal (HEK-293) cell lines by MTT assay. Compound (8) displayed higher activity than (4) with higher sensitivity against breast cancer cell line and lesser toxicity. The experimental data were further complemented by docking and absorption, distribution, metabolism, and excretion (ADME) studies.Communicated by Ramaswamy H. Sarma.

Functional Materials Based on Cyclometalated Platinum(II) ß-Diketonate Complexes: A Review of Structure-Property Relationships and Applications.

Square planar organoplatinum(II) complexes have garnered immense interest in the area of materials research. The combination of the Pt(II) fragment with mono-, bi- tri- and tetradentate organic ligands gives rise to a large variety of complexes with intriguing properties, especially cyclometalated Pt(II) complexes in which ligands are connected through covalent bonds demonstrate higher stability, excellent photoluminescence properties, and diverse applications. The properties and applications of the Pt(II)-based materials can be smartly fine-tuned via a judicious selection of the cyclometalating as well as ancillary ligands. In this review, attempts have been made to provide a brief review of the recent developments of neutral Pt(II) organometallic complexes bearing bidentate cyclometalating ligands and ß-diketonate ancillary ligands, i.e., (C^N)Pt(O^O) and (C^C)Pt(O^O) derivatives. Both small (monomeric, dimeric) and large (polymeric) materials have been considered. We critically assessed the role of functionalities (ligands) on photophysical properties and their impact on applications.