Problems in Commercial Kits of 25-Hydroxy Vitamin D and the Development of Simple, Robust and Faster HPLC Method.

Vitamin D is a lipid-soluble compound that plays a key role in bone mineral metabolism. The commercial current kits and several published assay methods (High-performance liquid chromatography (HPLC) and Immunoassay) are complicated due to the use of multiple reagents, larger sample volume, high backpressure, longer extraction time, evaporation under nitrogen after extraction, significant interference and antibody cross-reactivity. Here we report a new HPLC method for the determination of 25-hydroxyvitamin D2 (25-OHD2) and 25-hydroxyvitamin D3 (25-OHD3) that is simple (no evaporation), rapid (10-minute run time) and robust.

Accurate determination of Biotinidase activity in serum by HPLC and its utilization as second tier test for the confirmation of initial positive newborn screening results.

Diagnosis of Biotinidase deficiency (BTD) is extremely important to avoid several neurodevelopmental problems in early childhood. Colorimetric and fluorometric methods lack specificity and selectivity due to several interferences resulting in a high number of false positive results. We developed an HPLC method for BTD activity in serum with fluorescent detection.

and Xanthine Oxidase Inhibitory Activities of 3-Aryl-2- thioxo-2,3-dihydroquinazolin-4(1H)-one Derivatives.

Background: Hyperuricemia is associated with several disease conditions, such as atherosclerosis, arthritis, kidney stones, and many others. Xanthine oxidase (XO) is an enzyme that catalyzes the conversion of xanthine to uric acid. Hence, XO is a major therapeutic drug target in the treatment of hyperuricemia and associated disorders.

Upper Eyelid Reconstruction Surgeries; Comparison Of Outcomes Between Reverse Tenzel Flap Versus Cutler Beard Flap Procedure.

Background: Objective of this study was to compare Reverse Tenzel flap and Cutler Beard flap for upper eyelid defects.

Methods: This interventional study was carried out at occuloplasty department of LRBT (Layton Rahamatullah Benevoloent Trust), Karachi. Patients diagnosed with upper eye lid defect between 50 and 75 years were included after ethical approval from institutional ethical review committee and briefing patients about study dynamics.

New synthetic phenylquinazoline derivatives induce apoptosis by targeting the pro-survival members of the BCL-2 family.

Chemo-resistant cancer cells acquire robust growth potential through cell signaling mechanisms such as the down-regulation of tumor suppressors and the up-regulation of pro-survival proteins, respectively. To overcome chemo-resistance of cancer, small molecule drugs that interact with the cell signaling proteins to enhance sensitization of cancer cells toward cancer therapies are likely to be effective for the treatment of chemo-drug resistant cancer. To identify high potency small molecules, a series of ten novel phenylquinazoline derivatives were synthesized to determine their cellular effects in MCF-7 and MCF-7- cisplatin-resistant (CR) human breast cancer cells which led to the identification of two bioactive compounds, SMS-IV-20 and SMS-IV-40, that exhibited an elevated level of cytotoxicity against the human breast cancer cells and spheroid cells.

Potential anti-acanthamoebic effects through inhibition of CYP51 by novel quinazolinones.

Acanthamoeba spp. are free living amoebae which can give rise to Acanthamoeba keratitis and granulomatous amoebic encephalitis. The surface of Acanthamoeba contains ergosterol which is an important target for drug development against eukaryotic microorganisms.

An effort to find new αamylase inhibitors as potent antidiabetics compounds based on indole-based-thiadiazole analogs.

Inhibition of α-amylase enzyme is of key significance for the therapy of diabetes mellitus (DM). Numerous indole-based compounds have earlier been described for broad range of bioactivities. From our previous study, we knew that indole and thiadiazole are potent inhibitors of diabetics II.

Outcome Of Recurrent Macular Hole Closure With Amniotic Membrane Plug.

Background: The surgery of macular hole is a complex and intricate micro-surgery and chances of recurrence of macular hole are always high. Therefore, in order to provide a medium to close this hole, we carried out this research on subjects using amniotic membrane, in light of the studies being conducted around the world. This in turn led to benefitting the patients by improving their vision over time.

In vitro antiglycation and antioxidant properties of benzophenone thiosemicarbazones.

Fifteen benzophenone thiosemicarbazones were synthesized and their in vitro antiglycation activity was evaluated. The most active compound 2 (IC50 = 118.15±2.

Antiamoebic activity of 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one library against Acanthamoeba castellanii.

Acanthamoeba castellanii is a free-living amoeba which can cause a blinding keratitis and fatal granulomatous amoebic encephalitis. The treatment of Acanthamoeba infections is challenging due to formation of cyst. Quinazolinones are medicinally important scaffold against parasitic diseases.

Thymidine phosphorylase and prostrate cancer cell proliferation inhibitory activities of synthetic 4-hydroxybenzohydrazides: In vitro, kinetic, and in silico studies.

Over-expression of thymidine phosphorylase (TP) plays a key role in many pathological complications, including angiogenesis which leads to cancer cells proliferation. Thus in search of new anticancer agents, a series of 4-hydroxybenzohydrazides (1-29) was synthesized, and evaluated for in vitro thymidine phosphorylase inhibitory activity. Twenty compounds 1-3, 6-14, 16, 19, 22-24, and 27-29 showed potent to weak TP inhibitory activities with IC50 values in the range of 6.

Aryl Quinazolinone Derivatives as Novel Therapeutic Agents against Brain-Eating Amoebae.

and are protist pathogens that infect the central nervous system, causing primary amoebic meningoencephalitis and granulomatous amoebic encephalitis with mortality rates of over 95%. Quinazolinones and their derivatives possess a wide spectrum of biological properties, but their antiamoebic effects against brain-eating amoebae have never been tested before. In this study, we synthesized a variety of 34 novel arylquinazolinones derivatives (Q1-Q34) by altering both quinazolinone core and aryl substituents.

Novel antiacanthamoebic compounds belonging to quinazolinones.

We report one-pot synthesis of a series of new 3-aryl-8-methylquinazolin-4(3H)-ones (QNZ) and their antimicrobial activity against Acanthamoeba castellanii belonging to T4 genotype. A library of fifteen synthetic derivatives of QNZs was synthesized, and their structural elucidation was performed by using nuclear magnetic resonance (NMR) spectroscopy and electron impact mass spectrometry (EI-MS). Elemental analyses and high-resolution mass spectrometry data of all derivatives were found to be in agreeable range.

Synthesis, molecular docking and xanthine oxidase inhibitory activity of 5-aryl-1H-tetrazoles.

5-Aryl-1H-tetrazoles (1-24) were synthesized and screened for their xanthine oxidase (XO) inhibitory activity using allopurinol as standard inhibitor (IC = 2.0 ± 0.01 µM).

Coumarin sulfonates: As potential leads for ROS inhibition.

Coumarin sulfonates 4-43 were synthesized by reacting 3-hydroxy coumarin 1, 4-hydroxy coumarin 2and6-hydroxy coumarin 3 with different substituted sulfonyl chlorides and subjected to evaluate for their in vitro immunomodulatory potential. The compounds were investigated for their effect on oxidative burst activity of zymosan stimulated whole blood phagocytes using a luminol enhanced chemiluminescence technique. Ibuprofen was used as standard drug (IC=54.

Synthesis, molecular docking and α-glucosidase inhibition of 5-aryl-2-(6'-nitrobenzofuran-2'-yl)-1,3,4-oxadiazoles.

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 IC50 values in the range of 12.75±0.

Synthesis, α-glucosidase inhibitory, cytotoxicity and docking studies of 2-aryl-7-methylbenzimidazoles.

Benzimidazole analogs 1-27 were synthesized, characterized by EI-MS and (1)HNMR and their α-glucosidase inhibitory activities were found out experimentally. Compound 25, 19, 10 and 20 have best inhibitory activities with IC50 values 5.30±0.

4-Arylamino-6-nitroquinazolines: Synthesis and their activities against neglected disease leishmaniasis.

4-Arylamino-6-nitroquinazolines (2-25) were synthesized and evaluated for their leishmanicidal activities against Leishmania major promastigotes in vitro with IC50 values = 1.87-61.48 μM.

2-Arylquinazolin-4(3H)-ones: A new class of α-glucosidase inhibitors.

Twenty-five derivatives of 2-arylquinazolin-4(3H)-ones (1-25) were evaluated for their yeast (Saccharomyces cerevisiae) α-glucosidase inhibitory activities. All synthetic compounds, except 1 and 6, were found to be several hundred fold more active (IC50 values in the range of 0.3±0.

2-Arylquinazolin-4(3H)-ones: A novel class of thymidine phosphorylase inhibitors.

Thymidine phosphorylase (TP) over expression plays an important role in several pathological conditions, such as rheumatoid arthritis, chronic inflammatory diseases, psoriasis, and tumor angiogenesis. In this regard, a series of twenty-five 2-arylquinazolin-4(3H)-one derivatives 1-25 were evaluated for thymidine phosphorylase inhibitory activity. Six compounds 5, 6, 20, 2, 23, and 3 were found to be active against thymidine phosphorylase enzyme with IC50 values in the range of 42.

Evaluation of 2-indolcarbohydrazones as potent α-glucosidase inhibitors, in silico studies and DFT based stereochemical predictions.

2-Indolcarbohydrazones 1-28 were synthesized and evaluated for their α-glucosidase inhibitory potential. A varying degree of inhibitory potential with IC50 values in the range of 2.3±0.

Synthesis of new oxadiazole derivatives as α-glucosidase inhibitors.

Oxadiazole derivatives (6-28) having hydrazone linkage, were synthesized through condensation reaction between benzohydrazide 5 with various benzaldehydes. The oxadiazoles derivatives (6-28) were evaluated for their α-glucosidase inhibitory activity. The IC50 values for inhibition activity vary in the range between 2.

Synthesis and Biological Potential Assessment of 2-Substituted Quinazolin-4(3H)-ones as Inhibitors of Phosphodiesterase-I and Carbonic Anhydrase-II.

A library of twenty-five derivatives of 2-substituted quinazolin-4(3H)-ones 1-25 was synthesized and evaluated against phosphodiesterase-I (PDE) and carbonic anhydrase-II (CA). Compounds 17 (IC50 = 210.7 ± 2.

Synthesis of triazole Schiff bases: novel inhibitors of nucleotide pyrophosphatase/phosphodiesterase-1.

A series of Schiff base triazoles 1–25 was synthesized and evaluated for their nucleotide pyrophosphatase/phosphodiesterase-1 inhibitory activities. Among twenty-five compounds, three compounds 10 (IC50 = 132.20 ± 2.

Oxadiazoles and thiadiazoles: novel α-glucosidase inhibitors.

Oxadiazoles and thiadiazoles 1-37 were synthesized and evaluated for the first time for their α-glucosidase inhibitory activities. As a result, fifteen of them 1, 4, 5, 7, 8, 13, 17, 23, 25, 30, 32, 33, 35, 36 and 37 were identified as potent inhibitors of the enzyme. Kinetic studies of the most active compounds (oxadiazoles 1, 23 and 25, and thiadiazoles 35 and 37) were carried out to determine their mode of inhibition and dissociation constants Ki.