Biological activity of synthesized 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-mercapto-1, 3, 4-oxadiazole derivatives demonstrated by in silico and BSA binding studies

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

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.

interquartile relationship between polyherbal extract based lozenges linkus a phase four comparative randomised control trial

The aim of the study is to determine the efficacy of polyherbal linkus with the other pharmaceutical marketed syrup having Acefyllin Piperazine, Diphenhydramine group and Aminophylline Diphenhydramine group on the basis of interquartile ranges on children. It was open label multi centric randomize control trial. The study was conducted on different private schools of East and West Malir, Karachi Pakistan with the special approval from the school's honors. Informed consent and assents were taking before the enrollment of the study subjects. The study enrolled participants were 147 who evaluate on cough. Participants were divided into 3 interventional group according to the treatment regimen. One group of participant received Linkus Syrup however the 2[nd] group received Acefyllin Piperazine and 3[rd] group received Aminophylline Diphenhydramine group. The frequency of the cough on linkus syrup was considered to be achieved on the basis of interquartile relationship and impact has been observed on child and parent sleep and found significant [p <0.01].Poly herbal Linkus Syrup has the significant impact on cough frequency and associated problem on children and parent's sleep with minimum side effects [p<0.01] however the pharmacological treatments are considered to be more unwanted effects on human subjects

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.

Synthesis, spectral analysis and pharmacological study of N'- substituted-2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazides

ABSTRACT A series of molecules bearing multiple functional groups were synthesized to study their antibiotic effect against Gram-positive and Gram-negative bacteria and lipoxygenase activity as well. 2,4-Dimethylcarbolic acid (1) was refluxed with ethyl 2-bromoacetate to synthesize ethyl 2-(2,4-dimethylphenoxy)acetate (2). Compound 2 was converted to the corresponding hydrazide 3, again on refluxing with hydrazine. The compound 5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-thiol (4) was synthesized by the reaction of 3 and CS2 in the presence of KOH. Compound 4 was further converted to the corresponding ester 5 and then 2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazide (6). The final molecules N'-substituted-2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazide, 8a-m, bearing ether, 1,3,4-oxadiazole, thioether, hydrazone and azomethine functional groups were synthesized by stirring the aryl carboxaldehydes 7a-m with 6 in methanol at room temperature. The depicted structures of all synthesized molecules were corroborated by IR, 1H-NMR and EIMS spectral data analysis. 8m and 8i showed substantial antibacterial activity and lipoxygenase inhibitory activity, respectively.

Synthesis, spectral analysis and antibacterial evaluation of N'- substituted-2-[5-[3-chlorophenyl]-1,3,4-Oxadiazol-2- ylthio]acetohydrazide derivatives

The biological potential of N'-substituted-2-[5-[3-chlorophenyl]-1,3,4-Oxadiazol-2-ylthio]acetohydrazide [8ap] has been evaluated against bacterial strains of Gram-negative and Gram-positive bacteria. The multistep synthesis involved the conversion of 3-chlorobenzoic acid [1] to ethyl 3-chlorobenzoate [2], 3-chlorobenzohydrazide [3], 5-[3- chlorophenyl]-1,3,4-Oxadiazol-2-thiol [4], ethyl 2-[5-[3-chlorophenyl]-1,3,4-Oxadiazol-2-ylthio] acetate [5] and 2-[5-[3- chlorophenyl]-1,3,4-Oxadiazol-2-ylthio]acetohydrazide [6]. The last step involved the reaction of 6 and aryl aldehydes, 7a-p, in methanol to synthesize the Schiff bases, 8a-p, with better yields. The structures of all the molecules were corroborated by spectral analysis. The Schiff bases were further evaluated for the antibacterial activity and found to be moderately good inhibitors of bacterial strains of Gram-bacteria

Synthesis, spectral analysis and biological evaluation of Nalkyl/ aralkyl/aryl-4-chlorobenzenesulfonamide derivatives

New potent organic compounds were synthesized with an aim of good biological activities such as antibacterial and anti-enzymatic. Three series of sulfonamide derivatives were synthesized by treating N-alkyl/aryl substituted amines [2a-f] with 4-chlorobenzensulfonyl chloride [1] to yield N-alkyl/aryl-4-chlorobenzenesulfonamide[3af] that was then derivatized by gearing up with ethyl iodide [4], benzyl chloride [5] and 4-chlorobenzyl chloride [6] using sodium hydride as base to initialize the reaction in a polar aprotic solvent [DMF] to synthesize the derivatives, 7a-f, 8afand 9a-f respectively. Structure elucidation was brought about by IR, 1H-NMR and EIMS spectra for all the synthesized molecules which were evaluated for their antibacterial activities and inhibitory potentials for certain enzymes

Stress in female medical doctors; a cross-sectional study at tertiary care hospitals of Karachi

In present era stress remains a favorite subject of research especially in medical profession because with high competitive roles and responsibilities, this profession serves the need of mankind. Assessment of professional stress in female medical doctors employed at different tertiary care hospitals of Karachi, Pakistan. The cross-sectional non-experimental survey. Different tertiary care hospitals of Karachi. November, 2012 to July, 2013. Internationally validated and standardized questionnaire was used as survey tool for present research. It was distributed to total two hundred and twenty eight 228 female medical doctors. Total 191 respondents filled the research survey. 64.39% were MBBS, 20.42% were BDS and 15.18% were postgraduate respondents. Cronbach's alpha was 73.60%. Mean age of respondents was 29.32 +/- 6.96 years, average stress score was 12.09 +/- 4.33 with average years of experience were 4.58 +/- 5.57 years. Stress scores on the basis of demographic variables like age groups, experience, qualification and marital status showed average scores in range between10-12 units. However, high frequency of respondents scored moderate to severe stress when probed on the basis of levels of stress they have possess. Categorizing the equation for stress scores observed in the present survey as, MBBS respondents showed more stress units i.e., 12.50, BDS doctors have had 11.50 units stress and postgraduate respondents had 10 units stress scores. Results concluded that stress in female medical professionals is never underestimated as it is clearly indicated through present survey that all female respondents possess average job stress which need to address

Optimal and efficient management of mandibular fractures

The aim of the study was to find out whether eliminating intraoperative intermaxillary fixation from the management of mandibular fractures has any bearing on treatment outcomes. A retrospective study was carried out on 53 mandibular fractures treated at Margalla Institute of Health Sciences and its affiliated hospitals from June 2010 to December 2014. Successful bone healing, occlusion and complications were assessed in mandibular fractures treated with open reduction and internal fixation and without the use of intraoperative intermaxillary fixation. Minor wound dehiscence was seen in 7 patients. 3 patients required hardware removal due to subsequent hardware failure; however no case of nonunion was seen. Clinically significant malocclusion [Moderate: Grade 2] was seen in only one patient after 3 months. There were negligible and comparable number of postoperative complications. It was concluded 'hand holding' of the mandibular fractures as an alternative to the more traditional IMF/MMF through various means, a reliable and predictable way of fixation of mandibular fractures

Buccal fat pad flap in management of oroantral fistula

Many options are exercised to affect surgical management of oroantral fistulae. Postoperative wound dehiscence is not uncommon, and the surgical management of such fistulae often becomes increasingly difficult because of a lingering maxillary sinus infection. This was a retrospective study done on 23 patients in which a double layered technique, consisting of buccal fat pad in conjunction with buccal advancement flap was used for surgical closure of oroantral fistulae. Only 3 of the patients had had a failure of the closure. We recommend this technique because of its many advantages and low risk of complications

Third molars and angle fractures

Fractures of the mandibular angle are common and mandibular third molars are frequently implicated in their pathogenesis. The study was done to investigate this cause and effect relationship. The objectives were to measure the relationship between presence and status of mandibular third molar [M3] and mandibular angle fracture. Study design was descriptive. It was carried out in the Department of Oral and Maxillofacial Surgery, Punjab Dental Hospital, attached with de, Montmorency College of Dentistry, Lahore. 87 patients with clinical and radiographic diagnosis of mandibular fracture formed the study group. The predictor variable was the presence or absence of mandibular third molar. The outcome variable was the presence or absence of angle fracture. Hemi mandibles containing a third molar were seen to have a 2.3 times increased risk of having an angle fracture [p = 0.49] than a hemi mandible without a third molar. A significant association between third molar depth and risk of angle fractures was seen [p = 0.001]. The presence and depth of mandibular third molar is associated with an increased risk for mandibular angle fracture

Dental caries and pericoronitis associated with impacted mandibular third molars-a clinical and radiographic study

The most common impacted tooth is mandibular third molar and knowledge and assessment of its angulation pattern, position and depth in mandibular bone helps in better treatment planning and management of patients. The objective of this study was to enlist the frequency of dental caries and pericoronitis associated with different patterns of impacted mandibular third molars in different age groups and genders. A total of 250 patients with 393 impacted mandibular third molars seen in the Department of Oral and Maxillofacial Surgery, Punjab Dental Hospital, Lahore from October 2012 to March 2013 were included in the study. The age range of these patients was of 20 to 65 years. Patients were assessed by history, clinical and radiographic examination. Patterns of mandibular third molar impactions were assessed by using classification systems developed by Winter and Pell and Gregory on periapical radiographs. Pericoronitis was assessed by patient's history and clinical evaluation of mucosa surrounding the impacted mandibular third molars. Dental caries was assessed by clinical and radiographic evaluation. The most frequent pattern of impaction was mesioangular [37.6%], with Class II ramus relationship [53.2%] and Position A depth [62.8%]. Dental caries was seen in 38.53% of patients mostly associated with mesioangular, Position A, Class I molars. Pericoronitis was seen in 29.36% of patients mostly associated with distoangular, Position A or B, Class II molars. It was concluded that the patients having third molars with the unfavourable angulations, patterns and positions could be considered as the candidates for prophylactic removal of impacted mandibular third molars to prevent dental caries or pericoronitis. Moreover, early diagnosis of percoronitis and dental caries and proper management of third molar is necessary to prevent further consequences

Viability of costochondral graft in temporomandibular joint ankylosis

Temporomandibular joint [TMJ] ankylosis is a very distressing structural condition that causes severe facial disfigurement leading to pathopsychological stress. Impairment of speech, difficulty with mastication, rampant caries, poor oral hygiene, disturbances of facial growth and severely compromised airway are the leading consequences of TMJ ankylosis. Surgical intervention is the widely accepted treatment modality of TMJ ankylosis. Current study was performed on 30 patients for three years [2009-2012] department of Oral and Maxillofacial Surgery, Children Hospital and Department of Nuclear Medicine, Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore and costochondral graft was used to treat mandibular ankylosis. 21 [70%] patients were males and were divided into age groups of 2-5, 6-12 and 13-18 years. Regarding the side of mandible involved in male patients, unilateral ankylosis was found in 15[50%] and bilateral ankylosis were found in 6[20%] patients. Similarly in female patients, unilateral ankylosis was found in 7[23%] and bilateral ankylosis was seen in 2[7%] patients. Regarding post-operative monitoring of graft, bone scintigraphy was performed one week after the surgery and then after 12 weeks and 16 weeks to assess the viability and uptake of costochondral graft. Tc.99m MDP bone scan was performed in supine position with intravenous administration of 370MBq one week after the placement of graft. Results showed that out of 30 patients, CCG graft was viable in 28[93%] while it was non-viable in 2[7%] patients

Etiology of mandibular condylar fractures; a study from tertiary care hospital of Lahore

It is a cross sectional study conducted in a tertiary care hospital. Patients of condylar fracture reporting to oral and maxillofacial trauma center were evaluated radiographically [OPG, PA view and Lateral Oblique View] as well as clinically to record the etiology of mandibular condylar fractures. A total of 70 patients of 3 to 45 years of age were included in this study. The frequency of condylar fractures was higher in male of all age groups except for 11-20 years where females comprised of 55.5% of the cases. Among males, the highest frequency of fractures occurred in the third decade of life. Regarding the etiology of mandible condylar fractures, falls [45.71%] and RTA [40%] were found to be the most predominant causative factors, followed by industrial and occupational accidents [6%], Sports injuries [6%] and assault injuries [3%]. Falls were the etiologic factor in most of the cases which explains the association of falls with the mechanism of condylar injury. Road traffic accidents were the second common cause. Type 2 fractures which are low neck fractures with displacement were seen to be the most frequent