Chemistry

Cyclooxygenase (COX), a key enzyme playing crucial role in prostaglandin biosynthesis in Rheumatoid arthritis (RA) inflammation. For targeting COX-2 isoform, it is therefore interesting to design new molecule scaffolds with reduced side effects at gastric and renal levels. QSAR can modify the molecular structures for achieving the desired molecule with the proposed property, without experimental measurement. In the current study, we extend a published work that had been investiged the of 3, 5-diphenyl-2thioxo imidazolidin-4-ones derivatives as cyclooxygenase inhibitors. In this report, QSAR and regression analysis were used to predicate the cyclooxygenase inhibition activity of these derivatives. Moreover the cyclooxygenase inhibition activity for these molecules that was obtained experimentally is compared with the calculated ones. The cyclooxygenase inhibition activity of some of newly postulated 3, 5-diphenyl-2thioxo imidazolidin-4-ones derivatives showed a pronounced cyclooxygen...

QSAR can modify the molecular structures for achieving the desired molecule with the proposed property, without experimental measurement. In the current study, we extend a published work that had been investiged the caffeic acid derivatives as antibacterial and antifungal agents. In this report, QSAR and regression analysis were used to predicate the antimicrobial activity of these derivatives. Moreover, the antimicrobial activity for these molecules that was obtained experimentally is compared with the calculated ones. The antimicrobial activity of some of newly postulated caffeic acid derivatives showed a pronounced antimicrobial activity. QSAR and regression equations were useful in predicating the biologic activity of the old and postulated molecules with good validity.

Background. The outbreak of coronavirus disease 2019 (COVID-19) induced by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in China and spread to cover the entire world with an ongoing pandemic. The magnitude of the situation and the fast spread of the new and deadly virus, as well as the lack of specific treatment, led to a focus on research to discover new therapeutic agents. Aim. In this study, we explore the potential inhibitory effects of some active polyphenolic constituents of Rhus spp. (sumac) against the SARS-CoV-2 main protease enzyme (Mpro; 6LU7). Methods. 26 active polyphenolic compounds of Rhus spp. were studied for their antiviral activity by molecular docking, drug likeness, and synthetic accessibility score (SAS) as inhibitors against the SARS-CoV-2 Mpro. Results. The results show that all tested compounds of sumac provided good interaction with the main active site of SARS-CoV-2 Mpro, with better, lower molecular docking...

4-Phenylthiosemicarbazide (HPTS) was investigated as a new collector for the flotation of platinum(IV). The metal ion forms a (1: 2) pale green complex with HPTS in the aqueous solution. An intense clear green layer was formed, after flotation, by adding oleic acid (HOL) surfactant. The composition of the float is 1: 2 (Pt : HPTS). A highly selective and sensitive spectrophotometric procedure was proposed for the determination of microamounts of Pt(IV) as its floated complex. The flotation-determination method was achieved in the pH range 3-7. Beer's law was obeyed up to 6X 10-5 mol 1-1(11.7 ppm). The interferences from various foreign ions were avoided by adding excess HPTS. The molar absorptivities of Pt-HPTS and Pt-HPTS-HOL systems are 2X103 and 4.7X1031 moL1 cm-1 at 660 and 690 nm, respectively. The formation constants of the species formed in the presence and absence of HOL are calculated. The method was successfully applied to the determination of Pt(IV) in its allied materials. A mechanism of flotation is suggested.

4-Hydroxy-2-methyl-N-(2-thiazole)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (EX15) as nonsteroidal antiinflammatory drug (NSAIDs) of oxicam family has been synthesized bearing high selectivity for cyclooxygenase-2 (COX-2) inhibition and high ability to chelate with Cu(II) ions. The EX15-Cu(II) complex, and [Cu(EX15)(OAc)(H 2 O) 2 ], were synthesized and characterized by using elemental analysis, spectral (UV-Vis, IR), conductance, thermal and magnetic studies. Two equations were predicted using quantitative structure activity relationship (QSAR) and regression analysis for the COX-2 and COX-1 selectivity (microsomal assay) with a regression correlation (R) close to unity. Two techniques were used to investigate the validity of these equations; macrophage cell line (in vitro) selectivity and collagenadjuvant arthritis model in rats (in vivo) which showed a significant antioxidant, analgesic and antirheumatic effect for 4-hydroxy-2-methyl-N-(2-thiazole)-2H-1,2-benzothiazine-3-carboxamide-1,1dioxide and its Cu(II) complex, [Cu(EX15)(OAc)(H 2 O) 2 ].

Two new metal complexes derived from the reaction of 2-[(2-hydroxybenzoyl) 2,3,4a,5,10,10a-hexahydro-5,10[1 0 ,2 0 ]-benzenobenzo[g]phthalazine-1,4-dione] (HBPD) with Cu(II) and Zn(II) have been synthesized and characterized by using elemental analysis, spectral analysis (UV-Vis, IR, 1 H NMR, 13 C NMR), conductance, thermal analysis, and magnetic moments. The in vivo collagenadjuvant arthritis model in rats revealed a significant antioxidant, analgesic, and anti-rheumatic effects for HBPD and its copper and zinc complexes in comparison with standard piroxicam. The results showed that, the investigated Cu and Zn complexes have higher antiinflammatory activity than the free ligand.

A sensitive and selective flotation procedure for the separation of microamounts of Co(II), Ni(II) and Cu(II) separately or in admixture is described. The maximum separation rate (-1) for 0.1 mmol/L of each analyte is achieved using 1 mmol/L of both oleic acid (HOL) surfactant and 4-phenylthiosemicarbazide (HPTS) as a collector in the pH range 6-7. A method for the simultaneous separation and microdetermination of the analytes is elaborated, based on adding excess HPTS and floating the species with HOL at pH-6. The filtrate (which is clear brownish-yellow) obtained from the scum is used for the spectrophotometric determination of Co(II) at 350 nm. The formation constants of 1:1 and 1:2 [Co(II):HPTS] species are 6.9 x 10 5 and 1.22x 10 10 L molt , respectively. Beer's law is obeyed up to 9 µg/mL of Co(II) with a molar absorptivity of 1.15 x 10 4 L molt cm '. The precipitate in the scum layer is quantitatively collected, dissolved in aqua regia and aspirated directly into the flame for the (AAS) determination of Ni and Cu. The procedure is successfully applied to some natural water samples. A mechanism for the separation of the analytes is proposed.

Fig. 1. Reactive oxygen species (ROS) and reactive nitrogen species (RNS). Generation of oxygen as superoxide, hydrogen peroxide and hydroxyl radicals are involved in killing microorganisms by leukocytes. However, these same reactive oxygen species may damage cells (Babior et al, 1973). To counteract these oxidants, cells have several antioxidant enzymes including superoxide dismutase (SOD; EC 1.15.1.I), glutathione peroxidase (GSH-PX) and catalase. Eukaryotic cells have two forms of SOD; one found in the mitochondrial matrix, the manganese SOD (Mn-SOD), and another found predominantly in the cytosol, the copper-zinc SOD (Cu/Zn-SOD). Prokaryotes have another, iron SOD (Marklund, 1984). These enzymes dismutate superoxide to H 2 O 2 , which is then converted to water by either catalase or GHX-PX. The GSH-PX uses the reduced glutathione to convert H 2 O 2 to water as well as to convert lipid peroxide to lipid metabolites and eicosenoids. A delicate balance exists between expression of each SOD and GHX-PX to provide cellular resistance to oxidative stress (Kelner & Bagnell, 1990). It has been shown that in some cancers, reduced expression of Mn-SOD is due to mutations in the promoter of the gene, while in other types of cancer, reduced levels of Mn-SOD are due to abnormal methylation, loss of heterozygosity or mutation in the coding sequence (Hernandez-Saavedra & McCord, 2003). These different mechanisms cause the chaotic results about SOD in malignant tumors including gastric cancer, colorectal cancer and other gastrointestinal tumors (Hwang et al, 2007; Skrzydlewska et al, 2003; Tandon et al, 2004). Proteins are ubiquitous in all cells and tissues, constituting more than 50% of the dry weight of cells, and are susceptible to oxidative/nitrosative modifications. When reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels exceed the cellular antioxidant capacity, a deleterious condition known as oxidative/nitrosative stress occurs (Figures 2 & 3). It describes a status in which cellular antioxidant defenses are insufficient to keep the levels of ROS/RNS below a toxic threshold. This may be either due to excessive production o f R O S / R N S , l o s s o f a n t i o x i d a n t d e f e n s e s o r b o t h. U n c h e c k e d , e x c e s s i v e R O S / R N S generation can lead to the destruction of cellular components including proteins, and ultimately cell death via apoptosis or necrosis (Giustarini et al, 2004).

Three new metal complexes derived from Pd(II), Ru(III) and Zr(IV) with (E)-2-amino-N-(1-(2-aminophenyl)ethylidene)benzohydrazide (2-AAB) have been synthesized. The isolated complexes were characterized by elemental analyses, FT-IR, UV-Vis, ES-MS, (1)H NMR, XRD, thermal analyses (TGA and DTA) and conductance. The morphology and the particle size were determined by transmittance electron microscope (TEM). The results showed that, the ligand coordinates to Pd(II) in the enol form, while it coordinates to Ru(III) and Zr(IV) in the keto form. A square planar geometry is suggested for Pd(II) complex and octahedral geometries are suggested for Ru(III) and Zr(IV) complexes. The optical band gaps of the isolated complexes were measured and indicated the semi-conductivity nature of the complexes. The anti-inflammatory and analgesic activities of the ligand and its complexes showed that, Ru(III) complex has higher effect than the well known drug "meloxicam".

benzenobenzo[g]phthalazin-2-yl-N-ethylthioamide [6c] and their [Cu(6a-H)(OAc)], [Zn(6a-H)(OAc)], [Cu(6b-H)(H 2 O) 2 (OAc)]Á3H 2 O and [Zn(6b-H)(OAc)], [Cu 2 (6c-H)](OAc) 3 ]Á2H 2 O and [Zn(6c-H)(OAc)] complexes have been synthesized via a reaction between phthalazinedione 6a-c derivatives and the acetate salt of Cu(II) or Zn(II). These compounds were characterized by elemental analysis, spectra (UV-Vis, IR, 1 H NMR, 13 C NMR, ESR), conductance, thermal analysis and magnetic moments.

Complexes of Er(III), Gd(III), and La(III) with (2E,15E)-2-[1-(2-aminophenyl)ethylidineamino]-N 0-[1-(2aminophenyl)ethylidene]benzoic acid hydrazide (AEBH) have been synthesized. The isolated complexes were characterized by elemental analyses, thermal analyses (TGA, DTA), IR, 1 H NMR, 13 C NMR, ES-MS, TEM, and conductance measurements. The results indicated that the ligand coordinates to La(III), Gd(III), and Er(III) in the keto form as neutral pentadentate ligand. The particle size and morphology have been determined by TEM. In vivo pharmacological evaluation of the synthesized compounds in collagen II-Freund's adjuvant model proved the presence of anti-inflammatory and analgesic activities of these compounds. Gd(III) complex showed higher effect in comparison with the well-known drug meloxicam.

Drugs of cancer based upon ionizing radiation or chemotherapeutic treatment may affect breaking of DNA double strand in cell. DNA-PK enzyme has emerged as an attractive target for drug discovery efforts toward DNA repair pathways. Hence, the search for potent and selective DNA-PK inhibitors has particularly considered state-of-the art and several series of inhibitors have been designed. In this article, a novel benchmark DNA-PK database of 43 compounds was built and described. Ligand-based approaches including pharmacophore and QSAR modeling were applied and novel models were introduced and analyzed for predicting activity test for DNA-PK drug candidates. Based upon the modeling results, we gave a report of synthesis of fifteen novel 2-((8-methyl-2-morpholino-4-oxo-4H-benzo[e][1,3]oxazin-7yl)oxy)acetamide derivatives and in vitro evaluation for DNA-PK inhibitory and antiproliferative activities. These fifteen compounds overall are satisfied with Lipinski's rule of five. The biological testing of target compounds showed five promising active compounds 7c, 7d, 7f, 9e and 9f with micromolar DNA-PK activity range from 0.25-5 µM. In addition, SAR of the compounds activity was investigated and confirmed that the terminal aryl moiety was found to be quite crucial for DNA-PK activity. Moreover flexible docking simulation was done for the potent compounds into the putative binding site of the 3D homology model of DNA-PK enzyme and the probable interaction model between DNA-PK and the ligands was investigated and interpreted. .

A new molecular precursor Ca[SbO(SCH 2 COO)Cl H 2 O] was synthesized from the reaction of calcium thioacetate with SbCl 3 in (1:1) ratio. The precursor was characterized by elemental analyses, infrared spectra (IR), and thermal analyses (TGA). IR spectra indicated that thioacetate chelates Sb in a binegative bidentate manner via thiol sulfur and carboxylate oxygen after deprotonation. TGA results indicated that the precursor decomposes in three steps. Calcium antimonate (CaSb 2 O 6) was synthesized from the thermal decomposition of the molecular precursor at 250 C in air. The calcination product was characterized by X-ray diffractions (XRD), scanning electron microscope (SEM), and transmittance electron microscope (TEM). The results of X-ray diffractions indicated the formation of calcium antimonate nanoparticles which crystallizes in hexagonal system. The crystallite size was found to be 32 nm. Electron microscopes (SEM and TEM) indicated the formation of aggregates of spherical nanoparticles that forms rod like shape. The optical band gap (E g) measurements showed allowed direct electronic transition. The determined E g value is 3.9 eV, which is larger than the bulk.

Antiviral, Curcuminoids and Curcumin Derivatives SARS-CoV-2 is a newly emerging pandemic circulating worldwide causing millions of infections and many thousands of deaths. There are currently no specific therapies for treating coronavirus infections. Structure and screening results of important targets such as 3chymotrypsin-like protease (3CL pro) were thoroughly discussed. It is well known that curcumin and turmeric extracts showed prominent antiinflammatory, antiviral, antibacterial and anti-fungal activities, moreover they showed a positive effect on cytokine storm in many earlier studies. In the present study, with the aid of the molecular docking approach, we identify new possible inhibitors of SARS-CoV-2 using curcuminoids and curcumin derivatives. The identification of the M pro protease structure in COVID-19 provides a valuable chance to develop potential drug candidates for treatment. Considering the main protease in CoVs (3CL pro) (PDB ID 6LU7) and docking of our molecules in addition to some drugs for comparison purposes were carried out using the Molegro virtual docker. Curcuminoids and curcumin derivatives docked into 6LU7 active site revealed lower energy scores indicating more favored protein-ligand complexes. Curcuminoids and five curcumin derivatives showed to have the best potential to act as COVID-19 possible treatment. Further, in vitro and in vivo studies are necessary to examine their medicinal use for the identified molecules against coronavirus infection.

4-Hydroxy-2-methyl-N-(2-thiazole)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (EX15) as nonsteroidal antiinflammatory drug (NSAIDs) of oxicam family has been synthesized bearing high selectivity for cyclooxygenase-2 (COX-2) inhibition and high ability to chelate with Cu(II) ions. The EX15-Cu(II) complex, and [Cu(EX15)(OAc)(H 2 O) 2 ], were synthesized and characterized by using elemental analysis, spectral (UV-Vis, IR), conductance, thermal and magnetic studies. Two equations were predicted using quantitative structure activity relationship (QSAR) and regression analysis for the COX-2 and COX-1 selectivity (microsomal assay) with a regression correlation (R) close to unity. Two techniques were used to investigate the validity of these equations; macrophage cell line (in vitro) selectivity and collagenadjuvant arthritis model in rats (in vivo) which showed a significant antioxidant, analgesic and antirheumatic effect for 4-hydroxy-2-methyl-N-(2-thiazole)-2H-1,2-benzothiazine-3-carboxamide-1,1dioxide and its Cu(II) complex, [Cu(EX15)(OAc)(H 2 O) 2 ].

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation, pain, stiffness, and swelling in the affected joints typically with a symmetrical pattern on both sides of the body, which becomes more drastic and can also affect other organs and systems in the body. Thus, regular monitoring, follow-up of the disease, and exploring new metal-based therapy with minimum or no side effects are important challenges for managing the disease effectively. Methods: Complexes with the common formula [M(L)(OAc)] (M = Cu (II) or Zn (II)) and HL = 2-(-3-hydroxy-2-naphthoyl)-3,4,4a,5,10,10a-hexahydro-1H-5,10-benzeno-benzo[g]phthalazine-1,4-dione) were synthesized through a reaction between phthalazinedione derivative (HL) and Cu (II) and Zn (II) acetates. For synthesis and description of the HL, various elemental analyses, UV-Vis, infera red (IR), 1H-NMR, 13C-NMR, conductance, thermal gravimetric analysis (TGA), and magnetic moments were accurately performed. Additionally, the analgesic and anti-inflammatory activities of phthaline metal compounds were identified using adjuvant arthritis model comprising of forty-eight Sprague-Dawley rats (200-250 g). In that model, the rats were categorized into two main groups: control group (received sodium carboxymethyl cellulose (SCMC) solvent, n = 6) and arthertis group (n = 42). In arthertic group, the rats had been inoculated by the reagent of collagen-adjuvant arthritis into the left paw pad. After 45 days, the arthertic rats were further divided into seven different groups (n = 6 each): arthritic control, piroxicam-treated, zinc acetate-treated, copper acetate-treated, HL, copper complex-, and zinc complex-treated groups. Then for all treated and nontreated rats, paw edema, pain and pressure tolerance measurements, and mobilization tolerance (pain scoring) were identified as measures of improvement in the disease activity following the respective piroxicam as standard and metal compounds. Results: Phthalazine Copper (II) and Zinc (II) complexes showed anti-inflammatory action against rheumatoid arthritis as predicted by an equation with a regression correlation (R 2 = 0.95) calculated using quantitative structure activity relationship (QSAR) analysis. The anti-inflammatory activity of synthesized phthalazine metal complexes was supported by the application of docking analysis and in vivo model of collagen adjuvant arthritis in rats, respectively. The results of docking showed that phthalate-zinedine derivatives in keto form structure have a MolDock Score of-130.726 Kcal/mol and a MolDock Rerank Score of-96.2 Kcal/mol, respectively. These suggest that phthalazinedione derivatives in keto form are strong and anchored with a cyclooxygenase-2 active site, which consequently decreases the inflammatory pathways associated with the progression of rheumatoid arthritis (RH). RH rats treated with piroxicam reported significant (p = 0.001) anti-inflammatory activity with an improved bor RI and analgic effects measured by both increase in pain tolerance and decrease in pain score compared to RH-non-treated rats. In addition to that, significant (p = 0.01) analgesic and anti-inflammatory effects of the ligand (HL) and its copper and zinc complexes than piroxicam RH treated rats and non-treated RH rats, respectively, were reported when the complexes were applied to in vivo rat models with collagen adjuvant arthritis. Conclusions: Phthalazinedione derivative (HL), Cu (II), and Zn (II) acetates combined to treat rheumatoid arthritis (RH) show a good docking with inflammatory enzyme cyclooxygenase-2 (COX-2), with improved anti-inflammatory activities against RH as measured by docking and in vivo rat model of collagen adjuvant arthritis. In addition, the newly synthesized phthalazine metal complexes disclosed a significant anti-inflammatory and analgesic effect sequenced as [Zn(L)(OAc)] > HL > [Cu(L)(OAc)].

Background: phthalazine derivatives were reported to possess anticonvulsant , cardiotonic , antibacterial, analgesic , anti-inflammatory, and anti-microbial activity. In the current study, we applied the QSAR for prediction of newly phthalazinediones incorporating thioamide moiety aiming to reach a more potent anti-inflammatory and Analgesic agent. Methods: Phthalazinediones 10-15 have been synthesized through condensation of dibenzobarallene 3 with thiosemicarbazides 4-8. One equation was predicted using quantitative structure activity relationship (QSAR) and regression analysis for the anti-inflammatory activity with a regression correlation (R) close to unity. The docking studies were performed to investigate the biological trends of the organic compounds (thiol form) against cyclooxygenas-2 enzyme, which is a responsible inflammation mediator by using Molgro Virtual Docker (MVD) software. The anti-inflammatory activity and analgesic effect of the thioamides 10-15 were determined by collagen II-adjuvant induced paw edema test in rats. Results: Compounds 10, 11, 12, and 14, exhibited promising anti-inflammatory activity. Furthermore, in the pain scoring, compounds 10, 11 and 12 were found to be more effective than piroxicam and the order of the analgesic effect of the investigated compounds is as followed 14 >12 > 10 > 11 > 15. Conclusion: It is clear from the foregoing that the compound 14 is a promising compound if future pharmacological detailed studies. This is consistent with what has been predictable equation 1 in this study.

In an effort to establish new candidates with improved analgesic and anti-inflammatory activities, we reported here the synthesis and in-vivo analgesic and anti-inflammatory evaluation of various series of 2-substituted-3a,4,9,9a-tetrahydro-4,9-benzeno-benz[f]isoindole-1,3-diones: [4-Bromobutoxy] 6, 5-bromopentoxy 7, [4-(4-phenylpiperazin-1-yl)butoxy] 9, [5-(4-phenylpiperazin-1-yl)pentoxy] 10, 2-(2(4)-(4-phenylpiperazin-1-yl)-2-oxoethyl/4-oxobutyl 17, 19, [2(4)-(4-methylpiperazin-1-yl]-2-oxoethyl/ 4-oxobutyl 20, 22, [2(4)-morpholino-2-oxoethyl/4-oxobutyl] 23, 25, and 2(4)-(piperidin-1-yl)2-oxoethyl/ 4-oxobutyl) 26 and 28. The newly synthesized compounds were characterized by (IR, 1 H-, 13 C-NMR, and mass spectra). The representative compounds were evaluated as analgesic and anti-inflammatory activities. Compounds 9, 19, 22, 25, and 28 exhibited activities higher than the reference drug.

Long-term clinical usage of NSAIDs is associated with significant side effects of gastrointestinal lesions, bleeding, and nephrotoxicity. Therefore the discovery of new safer anti-inflammatory drugs represents a challenging goal for such a research area. The purpose of developing a QSAR model is to reduce the cost of the target designing by modifying the molecular structures for achieving the desired molecule with the proposed property, without experimental measurement. In the current study, we extend a published work that had been investigated the selenothiazole derivatives as anti-inflammatory activity and analgesic agents. In this report, One equation was predicted using quantitative structure activity relationship (QSAR) and regression analysis for the antiinflammatory activity with a regression correlation (R) close to unity(R 2~0 .97, R adj.>0.84). One technique was used to investigate the validity of this equation and collagen adjuvant arthritis model in rats (in vivo).. In the pain scoring, a compound 14 was found to be more effective than Meloxicam.

Recently, there have been a number of articles outlining the unique electrooptic properties that result from the incorporation of azo chromophores into high molecular weight materials. The properties of these materials are related to both the structure of the polymer and the bathochromicity of the dye. These types of polymers often exhibit nonlinear optical properties, which has led to their application in optical storage devices, electrooptic modulators, and second harmonic generators. A recent report has demonstrated the use of azo dyefunctionalized polymers as polyelectrolytes and described the property changes that may arise from the trans-cis isomerization of azo chromophores. 2 The UVvis properties of these azo compounds did not change upon inclusion into the polymers, and they showed promise as ultrathin multilayers and stimuli responsive materials.