Synthesis of new 2-{2,3-dihydro-1, 4-benzodioxin-6-yl[(4-methylphenyl) sulfonyl]amino}-N-(un/substituted-phenyl)acetamides as α-glucosidase and acetylcholinesterase inhibitors and their in silico study

The aim of the present research work was to investigate the enzyme inhibitory potential of some new sulfonamides having benzodioxane and acetamide moieties. The synthesis was started by the reaction of N-2,3-dihydrobenzo[1,4]-dioxin-6-amine (1) with 4-methylbenzenesulfonyl chloride (2) in the presence of 10% aqueous Na2CO3 to yield N-(2,3-dihydrobenzo[1,4]-dioxin-6-yl)-4-methylbenzenesulfonamide (3), which was then reacted with 2-bromo-N-(un/substituted-phenyl)acetamides (6a-l) in DMF and lithium hydride as a base to afford various 2-{2,3-dihydro-1,4-benzodioxin-6-yl[(4-methylphenyl)sulfonyl]amino}-N-(un/substituted-phenyl)acetamides (7a-l). All the synthesized compounds were characterized by their IR and 1H-NMR spectral data along with CHN analysis data. The enzyme inhibitory activities of these compounds were tested against a-glucosidase and acetylcholinesterase (AChE). Most of the compounds exhibited substantial inhibitory activity against yeast a-glucosidase and weak against AChE. The in silico molecular docking results were also consistent with in vitro enzyme inhibition data.

Incidence of contrast-induced nephropathy and its contributing factors after cardiac catheterization in type II diabetic patients

Objective: To evaluate the incidence of contrast-induced nephropathy [CIN] and its contributing factors after cardiac catheterization in type II diabetic patients. Study Design: Cross sectional study. Place and Duration of Study: Choudhary Pervaiz Ellahi Institute of Cardiology [CPEIC], Multan for six months, from Aug 2016 to Mar 2017

Material and Methods: This cross sectional study was conducted and completed in the department of cardiology Choudhary Pervaiz Ellahi Institute of Cardiology [CPEIC], Multan for six months [August 2016 to March 2017]. Before start of the study ethical approval was obtained from hospital ethical board/committee; informed consent was taken from patients and their attendants after complete information and they were also ensured about their confidentiality. All collected data was aligned and entered in a computer software SPSS version 23.1 and data was analyzed. Mean +/- SD values were calculated and presented for quantitative data variables like age, similarly frequency [percentages] were calculated and presented for qualitative variable data like gender. After stratification of data, student chi square test was used to see effect modification. A p-value

Results: A total number of 255 patients were included in the study. All patients were admitted for cardiac catheterization. Participants of the study were divided into two groups on the basis of CIN presence. Group A consisted of 210 patients who didn't develop contrast-induced nephropathy [CIN] after catheterization of coronary artery. Group B consisted of 45 patients of CIN after catheterization of coronary artery. It was found that incidence of CIN in diabetic patients with micro-albuminuria was 17.64% [n=45]

Conclusion: Observation of our study found that diabetic patients either with normal baseline creatinine are at an increased risk of developing CIN after angiography of coronary artery

Synthesis and in silico study of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives as suitable therapeutic agents

Abstract In the study presented here, a new series of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives was targeted. The synthesis was initiated by the treatment of different secondary amines (1a-h) with 4-bromomethylbenzenesulfonyl chloride (2) to obtain various 1-{[4-(bromomethyl)phenyl]sulfonyl}amines (3a-h). 2-Furyl(1-piperazinyl)methanone (2-furoyl-1-piperazine; 4) was then dissolved in acetonitrile, with the addition of K2CO3, and the mixture was refluxed for activation. This activated molecule was further treated with equi-molar amounts of 3a-h to form targeted 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives (5a-h) in the same reaction set up. The structure confirmation of all the synthesized compounds was carried out by EI-MS, IR and 1H-NMR spectral analysis. The compounds showed good enzyme inhibitory activity. Compound 5h showed excellent inhibitory effect against acetyl- and butyrylcholinesterase with respective IC50 values of 2.91±0.001 and 4.35±0.004 µM, compared to eserine, a reference standard with IC50 values of 0.04±0.0001 and 0.85±0.001 µM, respectively, against these enzymes. All synthesized molecules were active against almost all Gram-positive and Gram-negative bacterial strains tested. The cytotoxicity of the molecules was also checked to determine their utility as possible therapeutic agents.

Cleidocranial dysplasia- a case report and literature review

Cleidocranial dyspalsia is a rare congenital skeletal disorder, associated with hypoplasia or aplasia of clavicles, delayed closure of cranial sutures and fontanels, frontoparietal bossing, delayed exfoliation of primary dentition, delayed or failure of eruption of permanent teeth, and presence of multiple supernumerary teeth. The disorder is caused by mutation in the CBFA1 gene, on the short arm of chromosome 6p21. Estimated prevalence ofcleidocranial dysplasia is one per million, without gender or ethnic predilection. A multidisciplinary approach is often required for dental management of multiple supernumerary teeth. We report clinical and radiographic presentation and surgical management of multiple supernumerary teeth in an 11-year-old child with cleidocranial dysplasia.

Convergent synthesis of new N -substituted 2-{[5-(1H -indol-3-ylmethyl)-1, 3, 4-oxadiazol-2-yl]sulfanyl}acetamides as suitable therapeutic agents

abstract A series of N-substituted 2-{[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides (8a-w) was synthesized in three steps. The first step involved the sequential conversion of 2-(1H-indol-3-yl)acetic acid (1) to ester (2) followed by hydrazide (3) formation and finally cyclization in the presence of CS2 and alcoholic KOH yielded 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). In the second step, aryl/aralkyl amines (5a-w) were reacted with 2-bromoacetyl bromide (6) in basic medium to yield 2-bromo-N-substituted acetamides (7a-w). In the third step, these electrophiles (7a-w) were reacted with 4 to afford the target compounds (8a-w). Structural elucidation of all the synthesized derivatives was done by 1H-NMR, IR and EI-MS spectral techniques. Moreover, they were screened for antibacterial and hemolytic activity. Enzyme inhibition activity was well supported by molecular docking results, for example, compound 8q exhibited better inhibitory potential against α-glucosidase, while 8g and 8b exhibited comparatively better inhibition against butyrylcholinesterase and lipoxygenase, respectively. Similarly, compounds 8b and 8c showed very good antibacterial activity against Salmonella typhi, which was very close to that of ciprofloxacin, a standard antibiotic used in this study. 8c and 8l also showed very good antibacterial activity against Staphylococcus aureus as well. Almost all compounds showed very slight hemolytic activity, where 8p exhibited the least. Therefore, the molecules synthesized may have utility as suitable therapeutic agents.

resumo Uma série de acetamidas 2-{[5-(1H-indol-3-ilmetil)-1,3,4-oxadiazol-2-il]sulfanila} N-substituídas (8a-w) foi sintetizada em três fases. A primeira etapa envolveu a conversão sequencial de ácido 2-(1H-indol-3-il)acético (1) a éster (2), seguido por hidrazida (3) e, finalmente, a e ciclização na presença de CS2 e KOH alcoólico produziu 5-(1H-indol-3-il- metil)-1,3,4-oxadiazole-2-tiol (4). Na segunda etapa, aminas arílicas/aralquílicas(5a-w) reagiram com brometo de 2-bromoacetila (6​​), em meio básico, para se obter acetamidas 2-bromo-N-substituídas (7a-w). Na terceira etapa, estes eletrófilos (7a- w) reagiram com 4, para se obter os compostos alvo (8a-w). A elucidação estrutural de todos os derivados sintetizados foi realizada por 1H-NMR, IR e técnicas de espectrometria de EI-MS. Além disso, eles foram submetidos a triagem de atividade antibacteriana e hemolítica. Análise da inibição enzimática foi bem apoiada pelos resultados de docking molecular. Por exemplo, o composto 8q exibiu melhor potencial inibitório contra α-glicosidase, e os compostos 8g e 8b exibiram, comparativamente, melhor inibição contra butirilcolinesterase (BChE) elipoxigenase (LOX), respectivamente. Do mesmo modo os compostos 8b e 8c mostraram excelente potencial antibacteriano contra SalmonellaTyphi, semelhante ao do ciprofloxacino, antibiótico padrão usado neste estudo. Os compostos 8c e 8l também mostraram excelente potencial antibacteriano contra Staphylococcus aureus . Quase todos os compostos mostraram pequena atividade hemolítica, sendo que o composto 8p apresentou menor atividade. Assim, as moléculas sintetizadas podem ter a sua utilidade como agentes terapêuticos adequados.

Glomerular diseases outcome at one year in a tertiary care centre

To determine outcome in primary and secondary glomerular diseases at one year follow up. Study design is observational cohort, done in out-patient department, Dow Iinternational Medical College, DUHS. All information gathered on a proforma. All patients with dipstick positive proteinuria and clinical glomerular disease were included in study. Patients with no proteinuria were excluded so were patients with stage 5 CKD. Patients were followed for proteinuria and renal insufficiency at completion of one year follow up. Statistical analysis was done on SPSS version 16. Total number of patients who completed one year follow up was 173. Mean age of patients was 51.67 +/- 10.16 [range 15 to 75 years]. Ninety two [53.2%], were males and 81 [46.8%] were females, ratio being 1.1:1.0. Mean weight of our patients was 67.43 +/- 14.13 Kg, [35 to 107 kg]. Commonest cause of glomerular disease in our patient was diabetic nephropathy which was seen in 94.2% patients. Commonest associated problem with glomerular disease was hypertension seen in 66.5% of patients. Four out of 173 patients had stage 5 CKD at end of follow up at one year while quantitativ proteinuria remained same at one year follow up. One year follow up is critical for patients with glomerular disease associated with stage 4 CKD as progression to end stage renal failure may be seen within one year in these patients

Hemodialysis patients profile at Dow university of health sciences, Karachi, Pakistan

To determine the frequency of diseases contributing to End Stage Renal Failure [ESRF] and to determine the frequency of seropositivity for hepatitis B and hepatitis C in our patients. This is an observational study of two years duration from January 2012 till December 2013, done at Dow university of Health Sciences. Sample size is 189 by convenient method. Data collection is retrospective. Inclusion criteria includes all patients ever hemodialysed at DIMC with age 14 or above. Exclusion criteria is age below 14. Data maintained and analyzed on SPSS version 16. All categorical data in percentages and numeric data is given in frequencies and mean with Standard deviation. Total number of patients included in study were 189, Males were 94/189 [49.7%], females were 95/189 [50.3%], Male to female ratio was 0.98:1.0. Mean age was 51.88 +/- 15.2, range was 14-86 years. Patients started on Hemodialysis were found to have hypertension in 40.2%, both diabetes and hypertension was present in 42.8%, diabetes alone in 3.1% of patients as likely etiology of renal failure. Seropositivity for HBV was found 4/189[2.1%] and HCV in 31/189[16.4%] at initiation of Hemodialysis. Hypertension alone is an important disease found in patients with renal failure as likely cause followed by diabetes. Hepatitis C positivity at start of hemodialysis is 16%

Nutritional rickets: correlation between clinical, biochemical and radiological profile

To determine the correlation between clinical manifestations, biochemical and radiological profile in children with nutritional rickets. This is a cross-sectional study conducted at paediatric ward of a private sector health facility, Kutyana Memon Hospital Kharadar Karachi. A total of hundred patients aged 2 to 36 months with clinical suspicion of nutritional rickets were included in the study. A detailed history and examination was done and relevant investigations including serum calcium, phosphate, alkaline phosphatase and X-ray wrist joints were done to confirm the diagnosis. Data was analyzed and presented as percentages and frequencies. There were 63% males and 37% females. Majority of children were between 6 to 18 months of age, [49%] followed by 2-6 months [44%] and 18 to 36 months [07%]. Rachitic rosary was the most frequent clinical feature observed in 87% followed by widening of wrist joints in 76% cases. Serum calcium was low in 90% cases and serum alkaline phosphatase was increased in all patients. Serum phosphate was either low or normal in 44% cases each. Radiological findings were suggestive of rickets in 54% cases. Clinical and Biochemical markers are reliable indicators for diagnosis of nutritional rickets, which is more frequent between 2 to 18 months of age

Diagnosis of nasopharyngeal carcinoma on fine needle aspiration cytology of cervical lymph nodes

This study was carried out to see the sensitivity of Fine needle aspiration cytology [FNAC] in cervical lymph nodes in patients of carcinoma of the nasopharynx. This Study was carried at the Department of ENT and Head Neck Surgery of Khyber Teaching Hospital, Peshawar Pakistan from June 2003 to May 2005. Patients between the age of 30 and 70 years were included in the study. 25 patients having cervical lymphadenopathy were selected and divided into two groups A and B. Group A includes 20 patients which were undiagnosed cases of nasopharyngeal carcinoma. Out of them 17 patients have ENT Symptoms and 03 patients have only Cervical lymphadenopathy. Group B includes 05 patients who were post irradiated cases of Nasopharyngeal Carcinoma having detectable cervical lymphadenopathy. Fine needle aspiration was performed with 21 gauge needle attached with 20 ml syringe and smears were prepared. The cellularity in most of the smears was high 96%. Single scattered malignant cells were present in 92% of cases. The oval shaped vesicular neuclei were present in 92% of cases. In group B who had undergone radiotherapy showed one to three prominent nucleoli. FNAC of Cervical lymphnodes is an important diagnostic tool for the diagnosis of NPC, especially in those patients who have no ENT symptoms. It is also helpful in the follow up of post-irradiated patients