4-Oxycoumarinyl linked acetohydrazide Schiff bases as potent urease inhibitors.

Urease enzyme is responsible to catalyze the hydrolysis of urea into carbamate and ammonia. Then carbamate hydrolyzed to ammonia and carbon dioxide. Excess release of ammonia leads to increase pH in stomach that actually encourages the survival of Helicobacter pylori. H. pylori involves in various disorders most commonly peptic ulcer, pyelonephritis, hepatic coma, kidney stone formation, urolithiasis, and encephalopathy. Apart from many pharmacological properties, coumarin and Schiff bases are known to possess urease inhibitory activity. Therefore, these two pharmacologically important scaffolds are combined into single hybrid molecules to assess their potential as urease inhibitors. For this aim, N'-benzylidene-2-((2-oxo-2H-chromen-4-yl)oxy)acetohydrazide Schiff base derivatives 3-27 were synthesized by following a three step reaction strategy. Structures of all synthetic molecules were characterized by EI-MS, 1H-, and 13C NMR spectroscopic techniques. All molecules were assessed for urease inhibitory activity and found to possess a varying degree of inhibitory potential in the range of IC50 = 12.3 ± 0.69 to 88.8 ± 0.04 µM. Amongst the active analogs, compounds 7 (IC50 = 16.2 ± 0.11 µM), 9 (IC50 = 15.2 ± 0.14 µM), 10 (IC50 = 12.3 ± 0.69 µM), 12 (IC50 = 16.3 ± 0.45 µM), and 15 (IC50 = 17.6 ± 0.28 µM) were identified as potent inhibitors compared to standard urea (IC50 = 21.5 ± 0.47 µM). It is conferred from structure-activity relationship (SAR) that variation in inhibitory activity is due to different substitutions pattern on aryl ring. Moreover, molecular docking studies were carried out to understand the interactions of ligand with the active pocket of urease enzyme.

Metal-based biologically active compounds: Synthesis, spectral and antioxidant studies of transition metal complexes with hydrazone derivatives.

New series of Co+2, Ni+2, Cu+2 and Zn+2 complexes have been synthesized using a bio-active hydrazone compound 4-hydroxybenzaldehyde-N-(5-chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene), abbreviated as [HL]. Complexes were characterized using elemental analysis, FT-IR, UV-visible spectroscopy conductivity and magnetic susceptibility measurements. Results showed that the bi-dentate [HL] coordinated in a square planner manner with Cu+2 while for the rest of the M+2 ions, it coordinated in a octahedral fashion. Free ligand and its metal complexes were also studied for their antioxidant potential by employing two methods i.e. DPPH radical scavenging and reducing power assay. It was observed that the metal complexes were considerably more potent free radical scavenger and had better reducing abilities compared to the free ligand, furthermore, for both in vitro assays, metal complexes turned out to be better DPPH scavengers and had better reducing abilities than the standards used during biological assays.

Bioactive phenolic amides from Celtis africana.

Nine compounds have been isolated for the first time from Celtis africana, namely trans-N-coumaroyltyramine (1), trans-N-feruloyltyramine (2), trans-N-caffeoyltyramine (3), lauric acid (4), oleic acid (5), palmitic acid (6), lupeol (7), ß-sitosterol (8) and oleanolic acid (9), respectively. Their structures have been elucidated by different spectroscopic techniques. The isolated compounds were screened for their antioxidant, anti-inflammatory and acetylcholinestrease enzyme inhibitory activities. Compounds 1-3 showed significant antioxidant and anti-inflammatory activities and weak to moderate acetylcholinestrease enzyme inhibition activity.

Sorbicins A and B, new urease and serine protease inhibitory triterpenes from Sorbus cashmiriana.

Two new lupene-type triterpenes, sorbicins A and B, have been isolated from the chloroform-soluble fraction of the MeOH extract from the whole plant of Sorbus cashmiriana, and their structures were elucidated by spectroscopic techniques including 2D NMR. Both compounds displayed urease and α-chymotrypsin inhibitory potential.

Antioxidant and urease inhibitory C-glycosylflavonoids from Celtis africana.

Two new C-glycosylflavonoids celtisides A (1) and B (2) have been isolated from n-butanol-soluble fraction of Celtis africana, along with five known C-glycosylflavonoids vitexin (3), orientin (4), isoswertiajaponin (5), isoswertisin (6), and 2″-O-rhamnosyl vitexin (7) reported for the first time from this species. Their structures were assigned from 1D and 2D NMR spectra. These compounds were investigated for biological activities and showed significant antioxidant and urease inhibitory activities.

Conferin, potent antioxidant and anti-inflammatory isoflavone from Caragana conferta Benth.

Conferin (1), a new isoflavone, has been isolated from the ethyl acetate soluble fraction of Caragana conferta Benth. along with seven known compounds, namely biochanin A (2), p-hydroxybenzoic acid (3), 3,5-dimethoxybenzoic acid (4), ursolic acid (5), erythrodiol (6), pinoresinol (7), and syringresinol (8), reported for the first time from this species. The structure of the new isoflavone was deduced on the basis of spectroscopic studies. Compounds 1 and 2 were investigated for biological activities and showed significant anti-inflammatory activity in carrageenan induced paw edema of rats. Evaluation of antioxidant activity by the radical scavenging method indicated that compound 1 is a potent antioxidant while 2 is moderately active. It was also shown that the reducing capability of compound 2 was remarkably increased in a concentration dependent manner as compared to 1. Compound 1 showed moderate inhibitory activity against the enzyme lipoxygenase, while 2 showed weak activity.

Asphorodin, a potent lipoxygenase inhibitory triterpene diglycoside from Asphodelus tenuifolius.

Asphorodin (1), a new diglycoside, has been isolated from the ethyl acetate-soluble fraction of Asphodelus tenuifolius. It showed significant inhibitory activity against the enzyme lipoxygenase in a concentration-dependent manner. The Lineweaver-Burk and Dixon plots indicated that the nature of inhibition was non-competitive.

Structural determination of salsolins A and B, new antioxidant polyoxygenated triterpenes from Salsola baryosma, by 1D and 2D NMR spectroscopy.

Salsolins A (1) and B (2), the new triterpenes, have been isolated from the chloroform soluble fraction of Salsola baryosma along with 2alpha,3beta,23,24-tetrahydroxyurs-12-en-28-oic acid (3) reported for the first time from this species. Their structures have been assigned from 1H and 13C NMR spectra, DEPT and by 2D COSY, NOESY, HMQC and HMBC experiments. The compounds 1-3 showed significant antioxidant activity.

New butyrylcholinesterase inhibitory steroid and peroxy acid from Leucas urticifolia.

A new steroid leucisterol (1) and a new peroxy acid urticic acid (2) along with methoxybenzyl benzoate (3), 4-hydroxy benzoic acid (4), beta-sitosterol (5), and ursolic acid (6), have been isolated from the chloroform soluble fraction of the whole plant of Leucas urticifolia. Their structures were elucidated on the basis of nuclear magnetic resonance (1D and 2D NMR) spectral data. Leucisterol showed potent inhibitory activity against butyrylcholinesterase enzyme.

Leufolins A and B, potent butyrylcholinesterase-inhibiting flavonoid glucosides from Leucas urticifolia.

New flavonoidal glucosides leufolins A (1) and B (2), have been isolated from the ethyl acetate soluble fraction of the whole plants of Leucas urticifolia. Their structures were elucidated on the basis of extensive analysis of nuclear magnetic resonance (1D and 2D NMR) spectral data. Both of these compounds exhibited significant inhibitory potential against the enzyme butyrylcholinesterase.

Fuchs Heterochromic Iridocylitis: Clinical Characteristics and Outcome of Cataract Extraction with Intra Ocular Lens Implantation in a Kashmiri Population- A Hospital Based Study.

INTRODUCTION: Fuchs Heterochromic Iridocylitis (FHI) is a rare form of uveitis which is frequently complicated by cataract and glaucoma, but it does not show typical features of uveitis like pain, redness and posterior synechia. AIM: To study the clinical characteristics and outcome of cataract extraction with Intra Ocular Lens (IOL) implantation in patients with FHI. MATERIALS AND METHODS: The present prospective study was carried out in the Postgraduate Department of Ophthalmology, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Bemina from March 2012 to January 2015. The study included 33 eyes of 32 patients of FHI who underwent thorough clinical examination and cataract surgery with IOL implantation and were evaluated based on their visual outcome and intra and post-operative complications. Post-operative follow-up was done on 1st day, one week, one month, two month, six month and at twelve months. RESULTS: Mean age of our study group was 33.9 years (Range 18 to 65 years). No male or female preponderance was seen. There was bilateral involvement of eyes in only one case. Cataract and stellate keratic precipitates were present in all cases whereas, heterochromia was present in only six eyes (18.75%). Best Corrected Visual Acuity (BCVA) showed a significant improvement following cataract surgery (p<0.001). Post-operatively, 26 eyes (78.78%) showed an improvement of four lines or more (BCVA of > 6/12). Most common causes of decreased vision post-operatively were vitreous opacities in nine eyes (27.27%) followed by glaucoma in eight eyes (24.24%) and posterior capsular opacification in six eyes (18.18%). CONCLUSION: Cataract extraction with IOL lens implantation in FHI is a safe procedure associated with good visual prognosis and few complications. However, glaucoma is one of the main concerns and should be closely monitored both pre and post-operatively.