Combinatorial Chemistry & High Throughput Screening - Volume 23, Issue 7, 2020

Objective: Two novel Schiff bases named, 2-((2-Hydroxybenzylidene)amino)-4,5,6,7- tetrahydrobenzo[b] thiophene-3-carbonitrile (BESB1) and 2-((Furan-2-ylmethylene)amino)-4,5,6, 7-tetrahydro-benzo[b]thiophene-3-carbonitrile (BESB2) were synthesized. Methods: The structures were characterized based on CHN elemental analysis, mid-infrared (400– 4000 cm-1), Raman (100-4000 cm-1), 1H NMR, mass and UV-Vis spectroscopic measurements. In addition, quantum mechanical calculations using DFT-B3LYP method at 6-31G(d) basis set were carried out for both Schiff bases. Initially, we have carried out complete geometry optimizations followed by frequency calculations for the proposed conformational isomers; BESB1 (A–E) and BESB2 (F–J) based on the orientations of both CN and OH groups against the azomethine lonepair (NLP) in addition to the 3D assumption. Results: The computational outcomes favor conformer A for BESB1 in which the C≡N and OH moieties are cis towards the NLP while conformer G is preferred for BESB2 (the C≡N/furan-O are cis/trans towards the NLP) which was found consistent with the results of relaxed potential energy surface scan. Aided by normal coordinate analysis of the Cartesian coordinate displacements, we have suggested reliable vibrational assignments for all observed IR and Raman bands. Moreover, the electronic absorption spectra for the favored conformers were predicted in DMSO solution using TD-B3LYP/6-31G(d) calculations. Similarly, the 1H NMR chemical shifts were also estimated using GIAO approach implementing PCM including solvent effects (DMSO-d6). Conclusion: Proper interpretations of the observed electronic transition, chemical shifts, IR and Raman bands were presented in this study.

Aim and Objective: Wastewater treatment/remediation is a very important process that has a great environmental and economic impact. Therefore, it is crucial to innovate different methods to remove pollutants of different sources from wastewater. This work was conducted in order to study the removal of lead (Pb+2) from wastewater using microspheres of composites of sodium alginate, cellulose and chitosan, as well as using a cost-effective green route through composites of sodium alginate and dried water hyacinth. Materials and Methods: Molecular modeling at B3LYP/6-31g(d,p) was utilized to study sodium alginate, cellulose and chitosan. Sodium alginate was cross-linked with calcium chloride to form microspheres, then both sodium alginate/cellulose and sodium alginate/chitosan were also crosslinked as 50/50 to form microspheres. The roots of the aquatic plant water hyacinth in dry form were added to the cross-linked sodium alginate for up to 70%. SEM and FTIR were employed to study the surface of the prepared microspheres and their structures respectively. Atomic absorption spectroscopy was used to study the levels of Pb. Results: Molecular modeling indicated that the blending of such structures enhances their ability to bind with surrounding molecules owing to their ability to form hydrogen bonds. SEM results indicated that homogeneous structures of cellulose and chitosan are deformed when blended with sodium alginate, and FTIR confirmed the proper formation of the desired blends. Microspheres from sodium alginate showed the ability to remove Pb+2 from wastewater. SEM indicated further deformation in the morphology with the roughness of sodium alginate/water hyacinth microspheres, while FTIR confirmed the uniform matrices of the microspheres. The removal of Pb+2 was enhanced because of the addition of dried water hyacinth's roots. Conclusion: Modeling, experimental and kinetic data highlight sodium alginate/water hyacinth root as a green route to remediate Pb+2 from wastewater.

Background: The spinel ferrite nanoparticles, such as zinc, nickel, and cobalt ferrites have exceptional electronic and magnetic properties. Cobalt ferrite nanomaterial (CoFe2O4) is a hard material that reveals high magnetic, mechanical, and chemical stability. Aim and Objective: The objective of this research is to predict the corrosion behavior of cobalt ferrite (CoFe2O4) thin films deposited on different substrates (platinum Pt, stainless steel S.S, and copper Cu) in acidic, neutral, and alkaline medium. Materials and Methods: Cobalt ferrite thin films were deposited on platinum, stainless steel, and copper via electrodeposition-anodization process. After that, corrosion resistance of the prepared nanocrystalline cobalt ferrite on different substrates was investigated in acidic, neutral, and alkaline medium using open circuit potential and potentiodynamic polarization measurements. The crystal structure, crystallite size, microstructure, and magnetic properties of the ferrite films were investigated using a combination of XRD, SEM and VSM. Results: The results of XRD revealed a cubic spinel for the prepared cobalt ferrite CoFe2O4. The average size of crystallites was found to be about 43, 77, and 102 nm precipitated on platinum, stainless steel, and copper respectively. The magnetic properties of which were enhanced by rising the temperature. The sample annealed at 800oC is suitable for practical application as it showed high magnetization saturation and low coercivity. The corrosion resistance of these films depends on the pH of the medium as well as the presence of oxidizing agent. Conclusion: Depending on the obtained corrosion rate, we can recommend that, CoFe2O4 thin film can be used safely in aqueous media in neutral and alkaline atmospheres for Pt and Cu substrates, but it can be used in all pH values for S.S. substrate.

Aim and Objective: Platinum (II) and platinum (IV) of pyrophosphate complexes have been prepared and characterized to discover their potential as antitumor drugs. This study was conducted to prepare and characterize new ternary platinum (II) complexes with formamidine and pyrophosphate as an antitumor candidate. Materials and Methods: The complexes have been characterized by mass, infrared, UV-Vis. spectroscopy, elemental analysis, magnetic susceptibility, thermal analyses, and theoretical calculations. They have been tested for their cytotoxicity, which was carried out using the fastcolorimetric assay for cellular growth and survival against MCF-7 (breast cancer cell line), HCT- 116 (colon carcinoma cell line), and HepG-2 (hepatocellular cancer cell line). Results: All complexes are diamagnetic, and the electronic spectral data displayed the bands due to square planar Pt(II) complexes. The optimized complexes structures (1-4) indicated a distorted square planar geometry where O-Pt-O and N-Pt-N bond angles were 82.04°-96.44°, respectively. Results also show that all complexes are neutral, stable and non-hygroscopic and have noticeable cytotoxicity with IC50 (μM): 0.035-0.144 MCF-7(breast cancer cell line), 0.042-0.187 HCT-116 (colon carcinoma cell line), and 0.063-0.168 HepG-2 (hepatocellular cancer cell line). Moreover, the results show that the complex (4) has the best IC50 value. Conclusion: The complexes showed noticeable cytotoxicity and are considered as promising antitumor candidates for further applications.

Background: The Arisaema (Araceae) is a genus of approximately 180 perennial herbs widely distributed in the evergreen and deciduous forests. This genus (Arisaema) has been used as a medicinal agent since ancient times. Experimental investigations have shown a promising positive correlation with its folklore claim and this encourages us to report updated medicinal review (genus Arisaema) for future research. Objective: This review aimed to summarize the ethnobotany, folklore uses, chemistry and biological activities. Conclusion: The comprehensive literature on genus Arisaema indicates the presence of terpenoids, flavonoids, and glycosphingolipids as the principal chemical constituents. Additionally, phytosterols, alkaloids, carboline derivatives and miscellaneous compounds were documented in plants of genus Arisaema. Biological investigations led to the credentials of antioxidant, anticancer, insecticidal, antimicrobial, anthelmintic and hepatoprotective activities. Following, several plant species are promising candidates for the treatment of cancer, parasitic diseases and microbial infection complications. Though, a lot of facets of this genus like phytoconstituents identification, mechanistic profile, adverse effects and clinical studies are still quite limited. Thus, this systematic review may act as a powerful tool in future studies for promoting health benefits against various health hazards.

Aim and Objective: Lupus nephritis (LN) is one of the major complications of systemic lupus erythematosus (SLE). The specific mechanisms of pathogenesis, aggravation, and remission processes in LN have not been clarified but is of great need in the clinic. Using isobaric tags for relative and absolute quantitation (iTRAQ) technology to screen the functional proteins of LN in mice. Especially under intervention factors of lipopolysaccharide (LPS) and dexamethasone. Methods: Mrl-lps mice were intervened with LPS, dexamethasone, and normal saline (NS) using intraperitoneal injection, and c57 mice intervened with NS as control. The anti-ANA antibody enzyme-linked immunosorbent assay (ELISA) was used to verify disease severity. Kidney tissue is collected and processed for iTRAQ to screen out functional proteins closely related to the onset and development of LN. Western blot method and rt-PCR (real-time Polymerase Chain Reaction) were used for verification. Results: We identified 136 proteins that marked quantitative information. Among them, Hp, Igkv8-27, Itgb2, Got2, and Pcx proteins showed significant abnormal manifestations. Conclusion: Using iTRAQ methods, the functional proteins Hp, Igkv8-27, Itgb2, Got2, and Pcx were screened out for a close relationship with the pathogenesis and development of LN, which is worth further study.

Background: There are a number of protocols for Ullmann coupling–type S-arylation reactions, many of them suffer from the use of homogenous and often corrosive catalyst, cumbersome workup procedures, and long reaction times. Besides, many of these reagents are expensive and non-recoverable, leading to the generation of a large amount of toxic waste particularly when large-scale applications are considered. Objective: The aim of this study was to prepare a new Pd catalyst bonded on the surface of zeolite as a heterogeneous catalyst. Methods: A heterogeneous palladium catalyst has been prepared by immobilizing Pd ions on Clinoptilolite. This novel developed heterogeneous catalyst was thoroughly examined for Ullmann coupling–type S-arylation reaction using different bases, solvents and 0.003 mg of the catalyst. The structural and morphological characterizations of the catalyst were carried out using XRD, TGA, BET and TEM techniques. Results: Highly efficient heterogeneous palladium catalyst has been developed by immobilizing Pd ions on Clinoptilolite, as one of the most abundant naturally occurring zeolites for Ullmann Sarylation. By using this method, we provide an efficient way to a wide variety of substituted thiolic compounds. Moreover, the catalyst is easily recovered using simple filtration and reused for 5 consecutive runs. Conclusion: In this effort, we developed a new Pd catalyst bonded on the surface of zeolite as a substrate to prepare the heterogeneous catalyst. We demonstrate that this novel catalyst offers reliable and convincing data that may offer a valuable application in further developing the science and technology of Ullmann reaction protocols and allied industries. Additionally, the catalyst was reusable and kept its high activities over a number of cycles.

Aim and Objective: Esophageal squamous cell carcinoma (ESCC) is the most prevalent type of cancer with worldwide distribution and dismal prognosis despite ongoing efforts to improve treatment options. Therefore, it is essential to determine the prognostic factors for ESCC. Methods and Results: We determined KLRB1 to be a prognostic indicator of human ESCC. KLRB1 was expressed at low levels in ESCC patients. Based on the risk score, patients were divided into high and low-risk groups. High-risk patients showed a poor survival rate. The prediction model based on the N stage, sex, and KLRB1 was significantly better than that based on the N stage and sex. The modified prediction model showed a robust ROC curve with an AUC value of 0.973. The knockdown of KLRB1 inhibited the growth of human ESCC cells. KLRB1 regulated Akt, mTOR, p27, p38, NF-ΚB, Cyclin D1, and JNK signaling, which was consistent with the result of GSEA. Conclusion: KLRB1 is a potential prognostic marker for human ESCC patients.

Objective: Vasculitis is the basic pathological change of systemic lupus erythematosus (SLE). Radix Paeoniae Rubra (RPR), a traditional Chinese herb with the function of reducing blood stasis, has anti-inflammatory and immunoregulatory properties. This study explored the effects of RPR on the kidneys of lupus-like symptoms of mrl (MRL/lpr) mice from the perspective of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1). Methods: Eighteen MRL/lpr lupus model mice were randomly divided into three groups, the model control group, prednisone-treated group, and RPR-treated group, and 6 C57BL/ 6 mice were classified as a control group. After the mice had been treated for 12 weeks, the expression of ICAM-1, VCAM-1 and PECAM-1in the kidney was determined by immunohistochemistry and Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Results: After 12 weeks, there were significant differences in body weight in the model, prednisone and RPR groups compared with the normal group (P <0.05). Pathological observation: Compared with the model group, the proliferation of inflammatory cells infiltrated glomeruli and interstitial cells in prednisone and RPR groups were reduced, and renal pathological damage was reduced. Compared with the model group, urine protein level of prednisone and RPR groups were reduced with no significance (P> 0.05). The mRNA expression levels of ICAM-1 and VCAM-1 were significantly reduced in the prednisone group and RPR group compared with the model group (P <0.05 or P <0.01). Meanwhile, the immunohistochemistry expressions of ICAM-1 and VCAM- 1 expressed in the kidney were significantly reduced in the prednisone group and RPR group (P <0.01 or P <0.05). However, The mRNA expression level and the immunohistochemistry expressions of PECAM-1 expressed in the kidney were reduced in each treatment group (prednisone group and RPR group), but these differences were not significant (P>0.05). Conclusions: ICAM-1, VCAM-1 and PECAM-1 expression in the model group was found to be significantly increased. In addition, RPR could reduce the expression of ICAM-1, VCAM-1 and PECAM-1 in MRL/lpr lupus mice as effectively as prednisone, which may result in the dosage reduction of prednisone, thus decreasing the toxicity and improving the efficacy of prednisone - based treatment of SLE.