Synthesis, Characterization, Anti-Glycation, and Anti-Oxidant Activities of Sulfanilamide Schiff Base Metal Chelates.

The current study reports synthesis, structure establishment, anti-glycation, and anti-oxidant activities of ligand 4-[(2-hydroxynaphthalene-1-ylmethylene)-amino]-benzenesulfonamide (L) and its coordination compounds with Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) metal ions. The analytical techniques used (UV-Vis, FT-IR, CHN/S) confirmed the bidentate nature of the ligand, coordinating via O and N atoms in 2:1 ligand-to-metal ratio. The TG/DTA anylsis displayed that these compounds are thermally stable. Furthermore, the synthesized compounds were evaluated for their anti-glycation and antioxidant potential and showed significant activities with IC50 values range 184.11-386.34 µM and 37.05-126.27 µM, respectively. The Mn (IC50 = 184.11 ± 2.11 µM), Ni (IC50 = 211.26 ± 1.46 µM), Cu (IC50 = 254.56 ± 1.16 µM), and Zn (IC50 = 276.43 ± 2.14 µM) metal complexes exhibited substantial anti-glycation activity and comparatively better activity than the standard rutin (IC50 = 294.4 ± 1.50 µM), whereas Zn complex (IC50 = 37.05 ± 1.53 µM) also showed better DPPH radical scavenging activity than the standard tert-butyl-4-hydroxyanisole (IC50 = 44.7 ± 1.21 µM).

Synthesis, anti-diabetic and in silico QSAR analysis of flavone hydrazide Schiff base derivatives.

This study reports synthesis of flavone hydrazide Schiff base derivatives with diverse functionalities for the cure of diabetic mellitus and their a-glucosidase inhibitor and in silico studies. In this regard, Flavone derivatives 1-20 has synthesized and characterized by various spectroscopic techniques. These compounds showed significant potential towards a-glucosidase enzyme inhibition activity and found to be many fold better active than the standard Acarbose (IC50 = 39.45 ± 0.11 µM). The IC50values ranges 1.02-38.1 µM. Among these, compounds 1(IC50 = 4.6 ± 0.23 µM), 2(IC50 = 1.02 ± 0.2 µM), 3(IC50 = 7.1 ± 0.11 µM), 4(IC50 = 8.3 ± 0.34 µM), 5(IC50 = 7.4 ± 0.15 µM), 6(IC50 = 8.5 ± 0.27 µM) and 18 (IC50 = 1.09 ± 0.26 µM) showed highest activity. It was revealed that the analogues having -OH substitution have higher activity than their look likes. The molecular docking analysis revealed that these molecules have high potential to interact with the protein molecule and have high ability to bind with the enzyme. Furthermore, in silico pharmacokinetics, physicochemical studies were also performed for these derivatives. The bioavailability radar analysis explored that of all these compounds have excellent bioavailability for five (5) descriptors, however, the sixth descriptor of instauration is slightly increased in all compounds.Communicated by Ramaswamy H. Sarma.

Laser vs microdebrider eustachian tuboplasty for the treatment of chronic adult eustachian tube dysfunction: A systematic review.

OBJECTIVES: Multiple treatments are described in the literature for the treatment of chronic Eustachian tube dysfunction but high-level quality evidence seems missing to support these treatments. This systematic review aimed to determine and compare the safety and efficacy of Laser Eustachian tuboplasty and Microdebrider Eustachian tuboplasty as a treatment for long-term Eustachian tube dysfunction. DATA SOURCES: A total of 12 electronic databases were searched up to April 2018 for published and unpublished literature in the English language. References of included studies were checked. METHODS: A systematic review was undertaken. Outcomes assessed were: primary outcomes-subjective improvement in symptoms (ETDQ-7), audiometric improvement of hearing, improvement of negative middle ear pressure noticed in tympanometry, objective improvement of tympanic membrane retraction. Secondary outcomes were-the ability to auto-insufflate Eustachian tube i.e. Valsalva manoeuvre, improved quality of life, passive tubal opening, tubomanometry, swallowing test, reduction in mucosal inflammation of Eustachian tube orifice in the nose, complications from the procedure, the need for further procedures. Results are reported in a narrative synthesis as a meta-analysis was not possible due to heterogeneous data. RESULTS: Three studies were included. All included studies were small-scale case series (13-38 participants). Studies were conducted outside the UK. Subjective and objective improvement of Eustachian tube function was reported in all studies. But all included studies were at high risk of bias and subject to multiple limitations. No major complications were reported in either study. CONCLUSIONS: Based on current evidence, it is not possible to recommend the clinical use of either of these two interventions i.e. Laser or Microdebrider Eustachian tuboplasty. Lack of controlled studies was identified as a gap in the evidence. Future research should be directed toward designing randomised controlled trials. These trials should use strict standard methodology and reporting criteria. Future trials should make use of consensus statement document about Eustachian tube dysfunction definition, diagnostic methods, and outcome assessment criteria to design clinical trials.

Competitive Normalized Least-Squares Regression.

Online learning has witnessed an increasing interest over the recent past due to its low computational requirements and its relevance to a broad range of streaming applications. In this brief, we focus on online regularized regression. We propose a novel efficient online regression algorithm, called online normalized least-squares (ONLS). We perform theoretical analysis by comparing the total loss of ONLS against the normalized gradient descent (NGD) algorithm and the best off-line LS predictor. We show, in particular, that ONLS allows for a better bias-variance tradeoff than those state-of-the-art gradient descent-based LS algorithms as well as a better control on the level of shrinkage of the features toward the null. Finally, we conduct an empirical study to illustrate the great performance of ONLS against some state-of-the-art algorithms using real-world data.

Synthesis, ß-glucuronidase inhibition and molecular docking studies of cyano-substituted bisindole hydrazone hybrids.

The ß-glucuronidase, a lysosomal enzyme, catalyzes the cleavage of glucuronosyl-O-bonds. Its inhibitors play a significant role in different medicinal therapies as they cause a decrease in carcinogen-induced colonic tumors by reducing the level of toxic substances present in the intestine. Among those inhibitors, bisindole derivatives had displayed promising ß-glucuronidase inhibition activity. In the current study, hydrazone derivatives of bisindolymethane (1-30) were synthesized and evaluated for in vitro ß-glucuronidase inhibitory activity. Twenty-eight analogs demonstrated better activity (IC50 = 0.50-46.5 µM) than standard D-saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 µM). Compounds with hydroxyl group like 6 (0.60 ± 0.01 µM), 20 (1.50 ± 0.10 µM) and 25 (0.50 ± 0.01 µM) exhibited the most potent inhibitory activity, followed by analogs with fluorine 21 (3.50 ± 0.10 µM) and chlorine 23 (8.20 ± 0.20 µM) substituents. The presence of hydroxyl group at the aromatic side chain was observed as the main contributing factor in the inhibitory potential. From the docking studies, it was predicted that the active compounds can fit properly in the binding groove of the ß-glucuronidase and displayed significant binding interactions with essential residues.

Environmental Friendly Synthetic Modification of Amberlite XAD-2 Resin for the Removal of Highly Toxic Hexavalent Chromium from Water.

Amberlite XAD-2 functionalized by coupling through -C=N- spacer with isatin via an environmental friendly protocol. The modified resin was used for the evaluation of its sorption capacity towards toxic Cr (VI) ions using spectrophotometer. pH, volume, sorbent amount, initial concentration of Cr(VI) ions, and agitation time were optimized. The Freundlich and Dubinin- Radushkevich models gave better fit to isotherm data than Langmuir model. The evaluation of kinetic data indicated pseudo-first-order kinetics followed by sorption process. Thermodynamic parameters were also evaluated. Maximum recovery was obtained at 10 mL of 0.1M NaOH. Spiking methodology was used to confirm the validity of proposed method. The results revealed that developed method can be used for the removal of Cr(VI) ions efficiently from water, as well as reused for three cycles.

Design, synthesis, in vitro evaluation, molecular docking and ADME properties studies of hybrid bis-coumarin with thiadiazole as a new inhibitor of Urease.

Hybrid bis-coumarin derivatives 1-18 were synthesized and evaluated for their in vitro urease inhibitory potential. All compounds showed outstanding urease inhibitory potential with IC50 value (The half maximal inhibitory concentration) ranging in between 0.12 SD 0.01 and 38.04 SD 0.63 µM (SD standard deviation). When compared with the standard thiourea (IC50 = 21.40 ±â€¯0.21 µM). Among these derivatives, compounds 7 (IC50 = 0.29 ±â€¯0.01), 9 (IC50 = 2.4 ±â€¯0.05), 10 (IC50 = 2.25 ±â€¯0.05) and 16 (IC50 = 0.12 ±â€¯0.01) are better inhibitors of the urease compared with thiourea (IC50 = 21.40 ±â€¯0.21 µM). To find structure-activity relationship molecular docking as well as absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. All compounds were tested for cytotoxicity and found non-toxic.

Microbial Bioconversion: A Regio-specific Method for Novel Drug Design and Toxicological Study of Metabolites.

The methods of chemical structural alteration of small organic molecules by using microbes (fungi, bacteria, yeast, etc.) are gaining tremendous attention to obtain structurally novel and therapeutically potential leads. The regiospecific mild environmental friendly reaction conditions with the ability of novel chemical structural modification in compounds categorize this technique; a distinguished and unique way to obtain medicinally important drugs and their in vivo mimic metabolites with costeffective and timely manner. This review article shortly addresses the immense pharmaceutical importance of microbial transformation methods in drug designing and development as well as the role of CYP450 enzymes in fungi to obtain in vivo drug metabolites for toxicological studies.

Synthesis and molecular modelling studies of phenyl linked oxadiazole-phenylhydrazone hybrids as potent antileishmanial agents.

Molecular hybridization yielded phenyl linked oxadiazole-benzohydrazones hybrids 6-35 and were evaluated for their antileishmanial potentials. Compound 10, a 3,4-dihydroxy analog with IC50 value of 0.95 ± 0.01 µM, was found to be the most potent antileishmanial agent (7 times more active) than the standard drug pentamidine (IC50 = 7.02 ± 0.09 µM). The current series 6-35 conceded in the identification of thirteen (13) potent antileishmanial compounds with the IC50 values ranging between 0.95 ± 0.01-78.6 ± 1.78 µM. Molecular docking analysis against pteridine reductase (PTR1) were also performed to probe the mode of action. Selectivity index showed that compounds with higher number of hydroxyl groups have low selectivity index. Theoretical stereochemical assignment was also done for certain derivatives by using density functional calculations.

Synthesis of 6-chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives: Antidiabetic, antioxidant, ß-glucuronidase inhibiton and their molecular docking studies.

6-Chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives 1-26 were synthesized and characterized by various spectroscopic techniques. All these derivatives were evaluated for their antiglycation, antioxidant and ß-glucuronidase potential followed their docking studies. In antiglycation assay, compound 2 (IC50=240.10±2.50µM) and 4 (IC50=240.30±2.90µM) was found to be most active compound of this series, while compounds 3 (IC50=260.10±2.50µM), 6 (IC50=290.60±3.60µM), 13 (IC50=288.20±3.00µM) and 26 (IC50=292.10±3.20µM) also showed better activities than the standard rutin (IC50=294.50±1.50µM). In antioxidant assay, compound 1 (IC50=69.45±0.25µM), 2 (IC50=58.10±2.50µM), 3 (IC50=74.25±1.10µM), and 4 (IC50=72.50±3.30µM) showed good activities. In ß-glucuronidase activity, compounds 3 (IC50=29.25±0.50µM), compound 1 (IC50=30.10±0.60µM) and compound 4 (IC50=46.10±1.10µM) showed a significant activity as compared to than standard D-Saccharic acid 1,4-lactonec (IC50=48.50±1.25µM) and their interaction with the enzyme was confirm by docking studies.

Synthesis, In vitro and Docking Studies of New Flavone Ethers as α-Glucosidase Inhibitors.

We report herein the synthesis, α-glucosidase inhibition and docking studies for a series of 3-15 new flavones. A simple nucleophilic substitution reaction takes place between 3'hydroxyflavone (2) with halides to afford the new flavones. Chalcone (1), 3'hydroxyflavone (2) and the newly synthesized flavones (3-15) were being evaluated for their ability to inhibit activity of α-glucosidase. Compounds 2, 3, 5, 7-10 and 13 showed good inhibitory activity with IC50 values ranging between 1.26 and 36.44 µM as compared to acarbose (IC50 = 38.25 ± 0.12 µM). Compounds 5 (5.45 ± 0.08 µM), 7 (1.26 ± 0.01 µM) and 8 (8.66 ± 0.08 µM) showed excellent inhibitory activity, and this may be due to trifluoromethyl substitution that is common for these compounds. Compound 7, a 2,5-trifluoromethyl-substituted compound, recorded the highest inhibition activity, and it is thirty times better than the standard drug. Docking studies for compound 7 suggest that both trifluoromethyl substituents are well positioned in a binding pocket surrounded by Phe300, Phe177, Phe157, Ala278, Asp68, Tyr71 and Asp214. The ability of compound 7 to interact with Tyr71 and Phe177 is extremely significant as they are found to be important for substrates recognition by α-glucosidase.

Synthesis of novel flavone hydrazones: in-vitro evaluation of α-glucosidase inhibition, QSAR analysis and docking studies.

Thirty derivatives of flavone hydrazone (5-34) had been synthesized through a five-step reaction and screened for their α-glucosidase inhibition activity. Chalcone 1 was synthesized through aldol condensation then subjected through oxidative cyclization, esterification, and condensation reaction to afford the final products. The result for baker's yeast α-glucosidase (EC 3.2.1.20) inhibition assay showed that all compounds are active with reference to the IC50 value of the acarbose (standard drug) except for compound 3. Increase in activity observed for compounds 2 to 34 clearly highlights the importance of flavone, hydrazide and hydrazone linkage in suppressing the activity of α-glucosidase. Additional functional group on N-benzylidene moiety further enhances the activity significantly. Compound 5 (15.4 ± 0.22 µM), a 2,4,6-trihydroxy substituted compound, is the most active compound in the series. Other compounds which were found to be active are those having chlorine, fluorine, and nitro substituents. Compounds with methoxy, pyridine, and methyl substituents are weakly active. Further studies showed that they are not active in inhibiting histone deacetylase activity and do not possess any cytotoxic properties. QSAR model was being developed to further identify the structural requirements contributing to the activity. Using Discovery Studio (DS) 2.5, various 2D descriptors were being used to develop the model. The QSAR model is able to predict the pIC50 and could be used as a prediction tool for compounds having the same skeletal framework. Molecular docking was done for all compounds using homology model of α-glucosidase to identify important binding modes responsible for inhibition activity.

Synthesis of novel derivatives of 4-methylbenzimidazole and evaluation of their biological activities.

4-Methylbenzimidazole 1-28 novel derivatives were synthesized and evaluated for their antiglycation and antioxidant activities. Compounds 1-7 and 11 showed excellent activities ranged 140-280 µM, better than standard drug rutin (294.46 ± 1.50 µM). Compound 1-28 were also evaluated for DPPH activities. Compounds 1-8 showed excellent activities, ranging 12-29 µM, better than standard drug n-propylgallate (IC50 = 30.30 ± 0.40 µM). For superoxide anion scavenging activity, compounds 1-7 showed better activity than standard n-propylgallate (IC50 = 106.34 ± 1.6 µM), ranged 82-104 µM. These compounds were found to be nontoxic to THP-1 cells.

Phenoxyacetohydrazide Schiff bases: ß-glucuronidase inhibitors.

Phenoxyacetohydrazide Schiff base analogs 1-28 have been synthesized and their in vitro ß-glucouoronidase inhibition potential studied. Compounds 1 (IC50=9.20±0.32 µM), 5 (IC50=9.47±0.16 µM), 7 (IC50=14.7±0.19 µM), 8 (IC50=15.4±1.56 µM), 11 (IC50=19.6±0.62 µM), 12 (IC50=30.7±1.49 µM), 15 (IC50=12.0±0.16 µM), 21 (IC50=13.7±0.40 µM) and 22 (IC50=22.0±0.14 µM) showed promising ß-glucuronidase inhibition activity, better than the standard (D-saccharic acid-1,4-lactone, IC50=48.4±1.25 µM).

Synthesis, crystal structure, DFT studies and evaluation of the antioxidant activity of 3,4-dimethoxybenzenamine schiff bases.

Schiff bases of 3,4-dimethoxybenzenamine 1-25 were synthesized and evaluated for their antioxidant activity. All the synthesized compounds were characterized by various spectroscopic techniques. In addition, the characterizations of compounds 13, 15 and 16 were supported by crystal X-ray determinations and their geometrical parameters were compared with theoretical DFT calculations at the B3LYP level of theory. Furthermore, the X-ray crystal data of two non-crystalline compounds 8 and 18 were theoretically calculated and compared with the practical values of compounds 13, 15, 16 and found a good agreement. The compounds showed good DPPH scavenging activity ranging from 10.12 to 84.34 µM where compounds 1-4 and 6 showed stronger activity than the standard n-propyl gallate. For the superoxide anion radical assay, compounds 1-3 showed better activity than the standard.

An expeditious synthetic approach towards the synthesis of Bis-Schiff bases (aldazines) using ultrasound.

Aldazines (Bis-Schiff bases) 1-24 were synthesized using aromatic aldehydes (heterocyclic and benzaldehydes) and hydrazine hydrate under reflux using conventional heating and/or via ultrasound irradiation using BiCl3 as catalyst. Ultrasonication conditions with cat. BiCl3 proved to be an effective, environmentally friendly synthetic procedure. This methodology is robust in the presence of electron donating and electron withdrawing groups affording desired products with high yields (>95%) in just a couple of minutes vs. hours using conventional heating.

Synthesis, evaluation of antioxidant activity and crystal structure of 2,4-dimethylbenzoylhydrazones.

2,4-Dimethylbenzoylhydrazones 1-30 were synthesized by condensation reactions of 2,4-dimethylbenzoylhydrazide with various aromatic aldehydes and characterized. The assigned structures of compounds 10, 15 and 22 were further supported by single-crystal X-ray diffraction data. The synthesized compounds were evaluated for their in vitro DPPH radical scavenging activity. They exerted varying degree of scavenging activity toward DPPH radical with IC50 values between 25.6-190 µM. Compounds 1, 4, 2, 3, 7, and 6 have IC50 values of 25.6, 28.1, 29.3, 29.8, 30.0 and 30.1 µM respectively, showing better activity than an n-propyl gallate standard (IC50 value = 30.30 µM). For super oxide anion scavenging activity compounds 1, 2 and 3 with IC50 values of 98.3, 102.6, and 105.6, respectively, also showed better activity than the n-propyl gallate standard (IC50 value = 106.34 µM).

Liposarcoma of the spermatic cord.

A 43-years-old male patient presented through general practitioner with a complaint of right scrotal mass and was operated through inguinal approach. A 4 cm mass was excised and was found to be a liposarcoma of the spermatic cord upon histopathology, which is a diagnostic dilemma and very rare entity.