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A series of hydrazones 5a-i were synthesized by the condensation of hydrazides derived from dichlorophenylacetic acids with different aromatic aldehydes and ketones. Their structures were confirmed by spectroscopic data and elemental analysis. Hydrazones 5a-i were evaluated for α-glucosidase and urease inhibition activities. Five compounds exhibited potent α-glucosidase inhibitory potential with IC50 values 8.5 ± 0.3, 22.2 ± 0.78, 32.9 ± 1.5, 34 ± 2.4, and 170.6 ± 7.5 μM, respectively, which are many times better than that of the standard inhibitor acarbose ( IC50 = 840 ± 1.73 μM). Furthermore, molecular docking study was performed to explore the binding mode in the active sites of α-glucosidase and urease enzymes. [ABSTRACT FROM AUTHOR]

A series of barbiturates derivatives synthesized and screened for different set of bioassays are described. The molecular structures of compounds 5a, 5d, and 5f were solved by single-crystal X-ray diffraction techniques. The results of bioassay show that compounds 4a, 4b, 4c, 4d, 4e, 4f, and 4g are potent antioxidants in comparison to the tested standards, butylated hydroxytoluene (BHT), and N-acetylcysteine. Compounds 4a–4e (IC50=101.8±0.8–124.4±4.4 μM) and 4g (IC50=104.1±1.9 μM) were more potent antioxidants than the standard (BHT, IC50=128.8±2.1 μM). The enzyme inhibition potential of these compounds was also evaluated, in vitro, against thymidine phosphorylase, α-glucosidase, and β-glucuronidase enzymes. Compounds 4c, 4h, 4o, 4p, 4q, 5f, and 5m were found to be potent α-glucosidase inhibitors and showed more activity than the standard drug acarbose, whereas compounds 4v, and 5h were found to be potent thymidine phosphorylase inhibitors, more active than the standard drug, 7-deazaxanthine. All barbiturates derivatives (4a–4x, 4z, and 5a–5m) were found to be noncytotoxic against human prostate (PC-3), Henrietta Lacks cervical (HeLa) and Michigan Cancer Foundation-7 breast (MCF-7) cancer cell lines, and 3T3 normal fibroblast cell line, except 4y which was cytotoxic against all the cell lines. [ABSTRACT FROM AUTHOR]

• Synthesis of substituted quinoline based sulfonohydrazide. • Characterization of synthesized compounds. • Biological activity of synthesized compound as acetylcholinesterase inhibitors. • Biological activity of synthesized compound as butyrylcholinesterase inhibitors. • Structure activity relationship. • Molecular docking studies of potent inhibitors. A series of hydroxy‑quinoline-based sulfonohydrazide derivatives (1–16) were synthesized and their structures were elucidated by using various spectroscopic tools including 1HNMR, 13CNMR and HREI-MS and evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All synthesized derivatives showed the varied range of AChE and BuChE activities having IC 50 values ranging from 0.20 ± 0.01 to 11.60 ± 0.20 µM (against AChE) and 0.80 ± 0.05 to 22.70 ± 0.30 µM (against BuChE) as compared to standard drug Donepezil (IC 50 = 2.16 ± 0.12 µM & 4.5 ± 0.11 µM, respectively). Among the series, compounds 1, 8, and 10 were identified to be most potent, even more, active than standard drug having IC 50 values of 0.40 ± 0.05, 0.20 ± 0.01, 0.70 ± 0.05 µM (against AChE) and 0.80 ± 0.05, 0.80 ± 0.05, 2.10 ± 0.10 µM (against BuChE) respectively. Based on the substitution pattern around the aryl ring, structure-activity relationship (SAR) analysis was conducted for all synthesized derivatives. Additionally, the molecular docking method was created to investigate the mechanism of interactions between the scaffolds that are most active and the active sites of specific AChE and BuChE enzymes. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: In our effort directed toward the discovery of new anti-diabetic agent for the treatment of diabetes, a library of biscoumarin derivative 1–18 was synthesized and evaluated for α-glucosidase inhibitory potential. All eighteen (18) compounds displayed assorted α-glucosidase activity with IC50 values 16.5–385.9 μM, if compared with the standard acarbose (IC50 = 906 ± 6.387 μM). In addition, molecular docking studies were carried out to explore the binding interactions of biscoumarin derivatives with the enzyme. This study has identified a new class of potent α-glucosidase inhibitors. [Copyright &y& Elsevier]

[Display omitted] • Synthesis of new substituted thiadiazine thiones. • Anti-nociceptive activity of the synthesized compounds. • Major inflammatory enzymes, COX-2 and 5-LOX was examined. • Molecular docking COX-2 and 5-LOX was performed. A series of new thiadiazine derivatives including 2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) propanoic acids (a) and 4-methyl-2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) pentanoic acids (b) were synthesized by reacting primary alkyl/aryl amines with CS 2 , followed by reaction with formaldehyde and amino acids. The chemical structures of synthesized compounds were confirmed by 13C- NMR and 1H- NMR techniques. The inhibitory potential of major inflammatory enzymes, COX-2 and 5-LOX was examined. Moreover, anti-nociceptive and anti-inflammatory activities were evaluated in the in vivo thermally induced nociceptive, and carrageenan induced paw edema models in mice. The in-vitro results reflect that these compounds exhibited concentration dependent inhibition of COX-2 and 5-LOX. The tested compounds at 50 mg/kg showed significant effect on thermally induced pain, and reduced latency time (seconds) as compared to the vehicle treated animals. Moreover, tested compounds exhibited percent inhibition of paw edema in the carrageenan induced paw edema model in mice. Furthermore, the binding modes of the most active COX-2 and 5-LOX inhibitors were determined through computational methods. The computational study reflects that the docked compounds have high binding affinities for COX-2 and 5-LOX enzymes, which leads to inhibition of these enzymes. [ABSTRACT FROM AUTHOR]

• To synthesize of thiazole-based schiff base (1–20) along with characterization. • In vitro α-amylase and α-glucosidase enzymes study were carried out for all synthesized compounds. • Identification of a new α-amylase and α-glucosidase inhibitors. • Structure activity relationship established. • cytotoxicity against 3T3 mouse fibroblast cell line. • Molecular docking was carried to find interaction of inhibitors and enzymes. In search of potent antidiabetic agents here in this study a new series of thiazole-based Schiff base analogs (1–20) have been synthesized, characterized by 1HNMR, 13CNMR, HREI-MS and evaluated as dual inhibitor for α -glucosidase and α -amylase. All analogs of the series found active and exhibited variable degree of inhibitory potential ranging from 1.10 ± 0.10–17.20 ± 0.30 µ M as compared to reference drug acarbose IC 50 = for 9.80 ± 0.20 µ M α -glucosidase and from 0.90 ± 0.01 to 16.20 ± 0.30 µ M as compared to reference drug acarbose IC 50 = 10 0.30 ± 0.20 µ M for α -amylase. Compounds 3, 5, 6, 7, 14, 15, 16, 18 and 19 exhibited outstanding α -glucosidase as well as α -amylase inhibitory potential as compared to reference drug acarbose. Structure activity relationships SAR) have established for all the synthesized analogs. A molecular docking study has been conducted to develop an idea about binding interaction of compounds and enzymes. All synthesized compounds were tested for cytotoxicity and found nontoxic. [ABSTRACT FROM AUTHOR]

Abstract New tri- and diorganotin (IV) derivatives of 2,4-dichlorophenoxyacetic acid with general formula: R 3 SnL and R 2 SnL 2 : {Me 3 SnL (1), Bu 3 SnL (2), Me 2 SnL 2 (3), Bu 2 SnL 2 (4) and Oct 2 SnL 2 (5), L = 2,4-dichlorophenoxyacetate} have been synthesized and characterized in solid state by elemental and FT-IR analysis, whereas in solution state by 1H and 13C NMR spectroscopy. Compound 1 was also characterized by single crystal X-ray crystallography. The FT-IR data of compounds 1 – 5 confirm the bidentate binding mode of ligand with penta and hexa-coordinated arrangements around the Sn(IV) centre in solid state. The value of C Sn C angle for complexes 1 and 3 calculated from NMR (1H and 13C) data using Lockart's equation were 114.7° and 114.9°, respectively which falls in the range of 5-coordinated geometry. The DNA binding of synthesized compounds were studied via UV–Vis spectroscopy and viscometry resulting in an intercalative mode of interaction. Molecular docking analysis of the studied compounds also supports the results of the UV–vis and viscometry. Moreover, interaction of the synthesized compounds with a cationic surfactant i.e., cetyltrimethyl ammonium bromide (CTAB) has been studied by conductometric method. Enzyme inhibition activity against α-amylase and α-glucosidase was carried out and compound 3 was found to possess maximum inhibition (88.1% and 91.3%, respectively). The theoretical study also enforce the experimental data for enzyme inhibition of the compound 3 (docking score = −12.4096) by forming seven hydrogen bonds and two pi-H linkages with the Glu 276, Ala 278, Phe 300, Arg 312, Tyr 313, Asp 349, Asn 412, Phe 430 and Arg 439 residues of the binding pocket of the α-glucosidase. The potency of the compound 3 might be due to the presence of the strong electron withdrawing chloro group. IC 50 value of the brine shrimp activity revealed that triorganotin (IV) derivatives (1 and 2) were more toxic than their diorganotin (IV) analogues. Moreover, compound 2 has the MIC values of 12.5 μg/mL and 6.25 μg/mL against S. Aureus and M. Leuteus bacterial strains, respectively. Graphical abstract The novel organotin (IV) Carboxylates complexes interact with DNA via intercalative mode. Also they have strong tendency to interact with CTAB (surfactant) as indicated by higher CMC values and the resulting in micelle formation plays an important role in drug devilry. They show strong inhibitory potential against α -amylase and α -glucosidase. The DNA interaction and enzyme inhibition by Molecular Docking strongly support the experimental data. Highlights • Synthesis of Novel organotin (IV) Carboxylates. • Spectroscopic characterizations by FT-IR, NMR and single crystal X-ray. • Interaction with SS-DNA showing intercalation confirmed by UV-vis Spectroscopy and Molecular docking study. • Interaction with CTAB (surfactant). • Inhibition of alpha amylase and alpha glucosidase enzymes. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Schiff bases of tryptamine were synthesized. NTPDase inhibitory activity of synthetic derivatives have been evaluated. • Kinetic study of the three lead compounds has been performed. • In silico study of the most active compound was also carried out against NTPDas-1. Abstract Overexpression of NTPDases leads to a number of pathological situations such as thrombosis, and cancer. Thus, effective inhibitors are required to combat these pathological situations. Different classes of NTPDase inhibitors are reported so far including nucleotides and their derivatives, sulfonated dyes such as reactive blue 2, suramin and its derivatives, and polyoxomatalates (POMs). Suramin is a well-known and potent NTPDase inhibitor, nonetheless, a range of side effects are also associated with it. Reactive blue 2 also had non-specific side effects that become apparent at high concentrations. In addition, most of the NTPDase inhibitors are high molecular weight compounds, always required tedious chemical steps to synthesize. Hence, there is still need to explore novel, low molecular weight, easy to synthesize, and potent NTPDase inhibitors. Keeping in mind the known NTPDase inhibitors with imine functionality and nitrogen heterocycles, Schiff bases of tryptamine, 1 – 26 , were synthesized and characterized by spectroscopic techniques such as EI-MS, HREI-MS, 1H-, and 13C NMR. All the synthetic compounds were evaluated for the inhibitory avidity against activities of three major isoforms of NTPDases: NTPDase-1, NTPDase-3, and NTPDase-8. Cumulatively, eighteen compounds were found to show potent inhibition (Ki = 0.0200–0.350 μM) of NTPDase-1, twelve (Ki = 0.071–1.060 μM) of NTPDase-3, and fifteen compounds inhibited (Ki = 0.0700–4.03 μM) NTPDase-8 activity. As a comparison, the Ki s of the standard inhibitor suramin were 1.260 ± 0.007, 6.39 ± 0.89 and 1.180 ± 0.002 μM, respectively. Kinetic studies were performed on lead compounds (6 , 5 , and 21) with human (h -) NTPDase-1, -3, and -8, and Lineweaver-Burk plot analysis showed that they were all competitive inhibitors. In silico study was conducted on compound 6 that showed the highest level of inhibition of NTPDase-1 to understand the binding mode in the active site of the enzyme. [ABSTRACT FROM AUTHOR]

Nicotinic and isonicotinic thiosemicarbazide or hydrazine carbothioamides 3 – 27 were synthesized and the structures of synthetic compounds were elucidated by various spectroscopic techniques such as EI-MS, 1 H-, and 13 C NMR. Synthetic derivatives were evaluated for their urease inhibitory activity which revealed that except few all derivatives demonstrated excellent inhibition in the range of IC 50 values of 1.21–51.42 μM as compared to the standard thiourea (IC 50  = 21.25 ± 0.13 μM). Among the twenty-five synthetic derivatives nineteen 1 – 5 , 7 , 8 , 10 , 12 , 14 – 18 , 20 – 22 , 24 – 27 were found to be more active showing IC 50 values between 1.13 and 19.74 μM showing superior activity than the standard. Limited structure-activity relationship demonstrated that the positions of substituent as well as position of nitrogen in pyridine ring are very important for inhibitory activity of this class of compound. To verify these interpretations, in silico study was also performed. A good correlation was obtained between the biological evaluation of active compounds and docking study. [ABSTRACT FROM AUTHOR]

A series of 1-[(4′-chlorophenyl)carbonyl-4-(aryl)thiosemicarbazide derivatives 1 – 25 was synthesized and characterized by spectroscopic techniques such as EI-MS and 1 H NMR. All compounds were screened for urease inhibitory activity in vitro and demonstrated excellent inhibitory activity in the range of IC 50  = 0.32 ± 0.01–25.13 ± 0.13 μM as compared to the standard thiourea (IC 50  = 21.25 ± 0.13 μM). Amongst the potent analogs, compounds 3 (IC 50  = 2.31 ± 0.01 μM), 6 (IC 50  = 2.14 ± 0.04 μM), 10 (IC 50  = 1.14 ± 0.06 μM), 20 (IC 50  = 2.15 ± 0.05 μM), and 25 (IC 50  = 0.32 ± 0.01 μM) are many folds more active than the standard. Structure-activity relationship (SAR) was rationalized by looking at the effect of diversely substituted aryl ring on inhibitory potential which predicted that regardless of the nature of substituents, their positions on aryl ring is worth important for the potent activity. Furthermore, to verify these interpretations, in silico study was performed on all compounds and a good correlation was perceived between the biological evaluation and docking study of compounds. [ABSTRACT FROM AUTHOR]

Thymidine phosphorylase is an enzyme involved in pyrimidine salvage pathway that is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and gliostatin. It is enormously up regulated in a variety of solid tumors. Furthermore, surpassing of TP level protects tumor cells from apoptosis and helps cell survival. Thus TP is identified as a prime target for developing novel anticancer therapies. A new class of exceptionally potent isatin based oxadiazole ( 1 – 30 ) has been synthesized and evaluated for thymidine phosphorylase inhibitory potential. All analogs showed potent thymidine phosphorylase inhibition when compared with standard 7-Deazaxanthine, 7DX (IC 50  = 38.68 ± 1.12 µM). Molecular docking study was performed in order to determine the binding interaction of these newly synthesized compounds, which revealed that these synthesized compounds established stronger hydrogen bonding network with active site of residues as compare to the standard compound 7DX. [ABSTRACT FROM AUTHOR]

Current research is based on the synthesis of novel ( E )-4-aryl-2-(2-(pyren-1-ylmethylene)hydrazinyl)thiazole derivatives ( 3 – 15 ) by adopting two steps route. First step was the condensation between the pyrene-1-carbaldehyde ( 1 ) with the thiosemicarbazide to afford pyrene-1-thiosemicarbazone intermediate ( 2 ). While in second step, cyclization between the intermediate ( 2 ) and phenacyl bromide derivatives or 2-bromo ethyl acetate was carried out. Synthetic derivatives were structurally characterized by spectroscopic techniques such as EI-MS, 1 H NMR and 13 C NMR. Stereochemistry of the iminic double bond was confirmed by NOESY analysis. All pure compounds 2 – 15 were subjected for in vitro β -glucuronidase inhibitory activity. All molecules were exhibited excellent inhibition in the range of IC 50 = 3.10 ± 0.10–40.10 ± 0.90 μM and found to be even more potent than the standard d -saccharic acid 1,4-lactone (IC 50 = 48.38 ± 1.05 μM). Molecular docking studies were carried out to verify the structure-activity relationship. A good correlation was perceived between the docking study and biological evaluation of active compounds. [ABSTRACT FROM AUTHOR]

Twenty derivatives of 5-aryl-2-(6′-nitrobenzofuran-2′-yl)-1,3,4-oxadiazoles ( 1 – 20 ) were synthesized and evaluated for their α -glucosidase inhibitory activities. Compounds containing hydroxyl and halogens ( 1 – 6 , and 8 – 18 ) were found to be five to seventy folds more active with IC 50 values in the range of 12.75 ± 0.10–162.05 ± 1.65 μM, in comparison with the standard drug, acarbose (IC 50 = 856.45 ± 5.60 μM). Current study explores the α -glucosidase inhibition of a hybrid class of compounds of oxadiazole and benzofurans. These findings may invite researchers to work in the area of treatment of hyperglycemia. Docking studies showed that most compounds are interacting with important amino acids Glu 276, Asp 214 and Phe 177 through hydrogen bonds and arene-arene interaction. [ABSTRACT FROM AUTHOR]

Benzothiazole analogs ( 1 – 20 ) have been synthesized, characterized by EI-MS and 1 H NMR, and evaluated for urease inhibition activity. All compounds showed excellent urease inhibitory potential varying from 1.4 ± 0.10 to 34.43 ± 2.10 μM when compared with standard thiourea (IC 50 19.46 ± 1.20 μM). Among the series seventeen (17) analogs 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 16 , 17 , and 18 showed outstanding urease inhibitory potential. Analogs 15 and 19 also showed good urease inhibition activity. When we compare the activity of N -phenylthiourea 20 with all substituted phenyl derivatives ( 1 – 18 ) we found that compound 15 showed less activity than compound 20 having 3-methoxy substituent. The binding interactions of these active analogs were confirmed through molecular docking. [ABSTRACT FROM AUTHOR]

Thiadiazole derivatives 1 – 24 were synthesized via a single step reaction and screened for in vitro β -glucuronidase inhibitory activity. All the synthetic compounds displayed good inhibitory activity in the range of IC 50 = 2.16 ± 0.01–58.06 ± 1.60 μM as compare to standard d -saccharic acid 1,4-lactone (IC 50 = 48.4 ± 1.25 μM). Molecular docking study was conducted in order to establish the structure–activity relationship (SAR) which demonstrated that thiadiazole as well as both aryl moieties (aryl and N -aryl) involved to exhibit the inhibitory potential. All the synthetic compounds were characterized by spectroscopic techniques 1 H, 13 C NMR, and EIMS. [ABSTRACT FROM AUTHOR]

Benzimidazole analogs 1 – 27 were synthesized, characterized by EI-MS and 1 H NMR and their α -glucosidase inhibitory activities were found out experimentally. Compound 25 , 19 , 10 and 20 have best inhibitory activities with IC 50 values 5.30 ± 0.10, 16.10 ± 0.10, 25.36 ± 0.14 and 29.75 ± 0.19 respectively against α -glucosidase. Compound 6 and 12 has no inhibitory activity against α -glucosidase enzyme among the series. Further studies showed that the compounds are not showing any cytotoxicity effect. The docking studies of the compounds as well as the experimental activities of the compounds correlated well. From the molecular docking studies, it was observed that the top ranked conformation of all the compounds fit well in the active site of the homology model of α -glucosidase. [ABSTRACT FROM AUTHOR]

Isatin base Schiff bases ( 1–20 ) were synthesized, characterized by 1 H NMR and EI/MS and evaluated for α -glucosidase inhibitory potential. Out of these twenty ( 20 ) compounds only six analogs showed potent α -glucosidase inhibitory potential with IC 50 value ranging in between 2.2 ± 0.25 and 83.5 ± 1.0 μM when compared with the standard acarbose (IC 50 = 840 ± 1.73 μM). Among the series compound 2 having IC 50 value (18.3 ± 0.56 μM), 9 (83.5 ± 1.0 μM), 11 (3.3 ± 0.25 μM), 12 (2.2 ± 0.25 μM), 14 (11.8 ± 0.15 μM), and 20 (3.0 ± 0.15 μM) showed excellent inhibitory potential many fold better than the standard acarbose. The binding interactions of these active analogs were confirmed through molecular docking. [ABSTRACT FROM AUTHOR]

La 1− x Cr 0.7 x Eu 0.3 x FeO 3 nanoparticles were fabricated by micro-emulsion route. The value of x was kept in the range of 0.00 to 0.04. The synthesized nanoparticles were then characterized by X-ray diffraction (XRD), Fourier transform infra-red spectroscopy (FTIR) and scanning electron microscopy (SEM). The XRD confirmed the orthorhombic phase and estimated the crystallite size in the range of 30–90 nm. The nanoparticles estimated by SEM were in the range 60–100 nm. The XRD data was further supported by FTIR spectrum. The main FTIR bands observed were: Fe–O (418 cm −1 ), Cr–O (545 cm −1 ), La–O (570 cm −1 ) and Eu–O (416 cm −1 ). After structural elucidation, the La 1− x Cr 0.7 x Eu 0.3 x FeO 3 nanoparticles were subjected to magnetic parameters and dielectric behavior evaluation. The replacement of La 3+ ions, with Cr 3+ and rare earth Eu 3+ exhibited interesting magnetic and dielectric behavior. The LaFeO 3 nanoparticles without any dopants showed the paramagnetic behavior. However as the La 3+ was substituted by Cr 3+ and Eu 3+ , the ferromagnetic behavior was observed. Similarly the dielectric parameters were reduced by the replacement of La 3+ ions with Cr 3+ and Eu 3+ metal ions. The maximum magnetic parameters were observed for La 0.6 Cr 0.28 Eu 0.12 FeO 3 (Coercivity~0.04 T, Saturation magnetization ~0.728 emug −1 and Retentivity ~0.0.6783 emug −1 ). The maximum dielectric constant (23.52 at 1.5×10 −2 GHz) was observed for LaFeO 3 nanoparticles, while the minimum value of dielectric constant (10.32 at 1.5×10 −2 GHz) was exhibited by La 0.8 Cr 0.14 Eu 0.06 FeO 3 nanoparticles. [ABSTRACT FROM AUTHOR]