Impact of Nanoencapsulated Rosemary Essential Oil as a Novel Feed Additive on Growth Performance, Nutrient Utilization, Carcass Traits, Meat Quality and Gene Expression of Broiler Chicken.

This study evaluated the effect of free and nanoencapsulated rosemary essential oil (REO) as an antibiotic alternative in broiler diets on growth performance, nutrient digestibility, carcass traits, meat quality and gene expression. Four hundred twenty day-old commercial broiler chicks (VENCOBB) were randomly allocated to seven dietary treatments, each having four replicates of fifteen chicks. The dietary treatments comprised control (CON) fed a basal diet only, AB (basal diet + 10 mg enramycin/kg), CS (basal diet + 150 mg chitosan nanoparticles/kg), REOF100 and REOF200 (basal diet + 100 mg and 200 mg free REO/kg, respectively), and REON100 and REON200 (basal diet + 100 mg and 200 mg nanoencapsulated REO/kg, respectively). Overall (7-42 d), REON200 showed the highest (p < 0.001) body weight gain (1899 g/bird) and CON had the lowest gain (1742 g/bird), while the CS, REOF100 and REOF200 groups had a similar gain, but lower than that of the AB and REON100 groups. Feed intake was not affected by dietary treatments. Overall, the feed efficiency increased (p = 0.001) by 8.47% in the REON200 group and 6.21% in the AB and REON100 groups compared with the CON. Supplementation of REO improved (p < 0.05) dry matter and crude protein digestibility, with the highest values in REON100 and REON200. Ether extract, crude fiber, calcium and phosphorus digestibility values showed no difference among the groups. The dressing, breast, thigh % increased (p < 0.05) and abdominal fat % decreased (p < 0.001) more in the REON200 group than with other treatments and CON. In breast meat quality, water holding capacity and extract reserve volume increased (p < 0.05) while drip loss and cholesterol content decreased (p < 0.05) in REON100 and REON200. No change was observed in the breast meat color among dietary treatments and CON. The REON100 and REON200 groups had reduced (p < 0.05) meat lipid peroxidation as depicted by the decreased levels of TBARS, free fatty acids and peroxide value compared to other treatments and CON. The expression of the Mucin 2, PepT1 and IL-10 genes was upregulated (p < 0.001) and TNF-α downregulated (p < 0.001) by dietary addition of REO particularly in the nanoencapsulated form compared with the CON. In conclusion, nanoencapsulated REO, especially at 200 mg/kg diet, showed promising results as an antibiotic alternative in improving the performance, nutrient digestibility, carcass traits, meat quality and upregulation of growth and anti-inflammatory genes.

In-vitro and in-vivo antidiabetic activity of aerial parts of Aitchisonia rosea supported by phytochemical and GC-MS analysis.

Medicinal plants contain a wide variety of bioactive phytoconstituents which can serve as new therapeutic agents for several diseases. This study examines the antidiabetic potential of Aitchisonia rosea in alloxan-induced diabetic rats and identifies its bioactive phytoconstituents using GC-MS. In vitro, antidiabetic potential was established using the α-amylase inhibition assay. In vivo, antidiabetic potential was investigated by employing the oral glucose tolerance test (OGTT). GC-MS analysis was used to identify the bioactive phytoconstituents. The in vitro and in vivo tests showed that the aqueous extract of A. rosea possesses better antidiabetic potential. The α-amylase inhibition assay highlighted an IC50 value of 134.87µg/ml. In an oral glucose tolerance test, rats given an aqueous A. rosea extract significantly lowered their blood sugar levels significant reduction in the blood glucose concentration was observed in the oral glucose tolerance test in rats treated with the aqueous A. rosea extract. GC-MS investigation revealed many phytoconstituents, with serverogenin acetate and cycloheptasiloxane tetradecamethyl being important antidiabetic agents. This study found anti-diabetic properties in A. rosea extract. The phytochemical and GC-MS investigation also found serverogenin acetate and cycloheptasiloxane tetradecamethyl, which could be used to develop new antidiabetic drugs.

Antibacterial potential of Thymus linearis essential oil collected from Wasturwan mountain: A combination of experimental and theoretical studies involving in silico molecular docking simulation of the major compounds against Novobiocin-resistant mutant of DNA Gyrase-B.

Antibiotic resistant bacteria are immune to most antibiotics and are therefore very difficult to treat and in most cases lead to death. As such there is a pressing need for alternative and more efficient antibacterial drugs which can target these drug-resistant strains as well. The objective of this research work was to investigate the antibacterial properties of Thymus linearis essential oil (EO) against multiple disease-causing bacterial pathogens. Additionally, the study aimed to examine the molecular docking and molecular dynamic (MD) simulations of the primary components of the EO with the essential bacterial proteins and enzymes. Gas chromatography-mass spectrometry was employed to analyse the chemical composition of Thymus linearis EO. The initial screening for antibacterial properties involved the use of disc diffusion and microdilution techniques. Molecular docking studies were conducted utilising Autodock Vina. The outcomes were subsequently visualised through BIOVIA Discovery Studio. MD simulations were conducted using iMODS, an internet-based platform designed for MD simulations. The essential oil (EO) was found to contain 26 components, with thymol, carvacrol, p-cymene, and γ-terpinene being the primary constituents. The study findings revealed that Thymus linearis EO demonstrated antibacterial effects that were dependent on both the dose and time. The results of molecular docking studies revealed that the primary constituents of the EO, namely thymol, carvacrol, and p-cymene, exhibited robust interactions with the active site of the bacterial DNA gyrase enzyme. This finding provides an explanation for the antibacterial mechanism of the EO. The results indicate that Thymus linearis EO possesses potent antibacterial properties against the MDR microorganisms. Molecular docking analyses revealed that the essential oil's primary components interact with the amino acid residues of the DNA-Gyrase B enzyme, resulting in a favourable docking score.

Determination of Hypoglycemic, Hypolipidemic and Nephroprotective Effects of Berberis Calliobotrys in Alloxan-Induced Diabetic Rats.

Many plants of the Berberis genus have been reported pharmacologically to possess anti-diabetic potential, and Berberis calliobotrys has been found to be an inhibitor of α-glucosidase, α-amylase and tyrosinase. Thus, this study investigated the hypoglycemic effects of Berberis calliobotrys methanol extract/fractions using in vitro and In vivo methods. Bovine serum albumin (BSA), BSA-methylglyoxal and BSA-glucose methods were used to assess anti-glycation activity in vitro, while in vivo hypoglycemic effects were determined by oral glucose tolerance test (OGTT). Moreover, the hypolipidemic and nephroprotective effects were studied and phenolics were detected using high performance liquid chromatography (HPLC). In vitro anti-glycation showed a significant reduction in glycated end-products formation at 1, 0.25 and 0.5 mg/mL. In vivo hypoglycemic effects were tested at 200, 400 and 600 mg/kg by measuring blood glucose, insulin, hemoglobin (Hb) and HbA1c. The synergistic effect of extract/fractions (600 mg/kg) with insulin exhibited a pronounced glucose reduction in alloxan diabetic rats. The oral glucose tolerance test (OGTT) demonstrated a decline in glucose concentration. Moreover, extract/fractions (600 mg/kg) exhibited an improved lipid profile, increased Hb, HbA1c levels and body weight for 30 days. Furthermore, diabetic animals significantly exhibited an upsurge in total protein, albumin and globulin levels, along with a significant improvement in urea and creatinine after extract/fractions administration for 42 days. Phytochemistry revealed alkaloids, tannins, glycosides, flavonoids, phenols, terpenoids and saponins. HPLC showed the presence of phenolics in ethyl acetate fraction that could be accountable for pharmacological actions. Therefore, it can be concluded that Berberis calliobotrys possesses strong hypoglycemic, hypolipidemic and nephroprotective effects, and could be a potential therapeutic agent for diabetes treatment.

Modular and Computational Access to Innocuous Multistep Metal-Free Synthesis of 1,3,4-Oxadiazoles as Enzyme Inhibitors.

An array of 1,3,4-oxadiazole hybrids, 7a-s, structurally intriguing cores with potential in natural product synthesis and drug discovery, have been synthesized using innovative comparable conventional and microwave-assisted protocols. The synthesis was performed by the reaction of secondary amine-based acetamides, 6a-s, as the electrophile and piperidine-based oxadiazoles as the nucleophile, 3, under the metal-free reaction conditions. High yield in minimum time with highest purity was obtained by the microwave-irradiated method instead of the conventional one. The structural elucidations were made through infrared, 1H NMR, 13C NMR, and elemental analysis studies. The whole array of synthesized compounds, 7a-s, was evaluated for their potential against α-glucosidase and butyryl cholinesterase (BChE) enzymes. Natural bond orbital and structural optimizations were made by using the B3LYP method and the basis set of 6-311++G(d,p). Frontier molecular orbitals and molecular electrostatic potential were calculated at the same level of selected compounds as potential candidates against BChE and α-glucosidase enzymes utilizing the time-dependent density functional theory. Fifteen compounds out of 19 were observed to be active against α-glucosidase enzyme in comparison with acarbose as the reference standard and 7 against the BChE enzyme compared to eserine as the reference standard. The highest potential of compound 7j against BChE is well correlated by the higher binding interaction with target protein as -10.2, calculated by docking studies. The recruited compounds against both enzymes could be the best anti-enzymatic drugs and part of drugs discovery programs after further analysis.

Primary oesophageal tuberculosis presenting with dysphagia: A rare scenario.

Dysphagia is a clinical manifestation with great consequences. Prompt and early diagnosis is the key to long-term management. Despite tuberculosis (TB) being common in developing countries, primary oesophageal TB is still a very rare disease. Oesophageal manifestations are almost exclusively a result of direct extension from adjacent mediastinal structures. We report a case of an immune-competent man presenting with dysphagia due to primary oesophageal TB.

Plant based natural products as potential ecofriendly and safer biopesticides: A comprehensive overview of their advantages over conventional pesticides, limitations and regulatory aspects.

The commercially used synthetic pesticides have been proven to be toxic not only to humans and other animals, but also to non-target plant, the surrounding organisms around the plant, and the environment. There are also increased concerns regarding the development of pest resistance towards these synthetic pesticides. As such, biopesticides, which are defined as the certain kinds of pesticides derived from natural sources such as plants, bacteria, fungi, animals and some minerals, are potential alternative pesticides and are gaining increasing attention. Biopesticides are safer and eco-friendly pesticides used for pest management. Among these, plant-based biopesticides constitute a small but important group of biopesticides. Plant based extracts and essential oils have been particularly used in the management of insects exhibiting a variety of anti-insecticidal mechanisms. Their chemical compositions are very complex and as such acquiring resistance by the pest against such biopesticide is very difficult. As far as their mechanism of action is concerned, these can act as insect repellants, insect attractants, or anti-feedants. They can also inhibit respiration or they can obstruct the host plant identification. These insecticides can inhibit oviposition and decrease adult emergence by ovicidal and larvicidal effects. Some of the essential oil based insecticides have even been commercialized for use. However, there are some limitations that restrict the widespread use of such biopesticides. These limitations include cost, difficulties in production, gentle action, and dearth of appropriate biopesticide formulations. As far as their regulations are concerned, it is still a problem in many countries further halting biopesticide use. But one thing is clear that biopesticides do have a promising future due to their eco-friendly nature and unique chemical compositions and unique mode of action.

Synthesis, Characterization, and Enzyme Inhibition Properties of 1,2,4-Triazole Bearing Azinane Analogues.

Considering the importance of acetylcholine esterase (AChE, BchE) and α-glucosidase in the treatment of Alzheimer's disease and diabetes mellitus, the synthesis of novel azinane triazole-based derivatives as effective acetylcholinesterase (AchE), α-glucosidase, urease, lipoxygenase (LOX), and butyrylcholinesterase (BChE) inhibitors is described. Azinane analogue (2) was merged with 1,2,4-triazole to acquire 1-(4-toluenesulfonyl)-4-(3-mercapto-4-methyl-4H-1,2,4-triazol-5-yl) piperidine (8) through a list of intermediates including 1-(4-toluenesulfonyl)-4-(ethoxycarbonyl) piperidine (3), 1-(4-toluenesulfonyl)-4-(2-hydrazinocarbonyl)piperidine (5), and 1-(4-toluenesulfonyl)-4-[1-(methyl amino thiocarbonyl)-2-hydrazinocarbonyl]piperidine (7). The target molecules, 1-(4-toluenesulfonyl)-4-[3-(N-alkyl/phenyl/aryl-2-ethanamoyl thio)-4-methyl-4H-1,2,4-triazol-5-yl] piperidine (12a-o), were achieved through the reaction of 8 with N-alkyl/phenyl/aryl-2-bromo ethanamides (11a-o) as electrophiles. These electrophiles were accomplished by a benign reaction of alkyl/phenyl/aryl amines (9a-o) and 2-bromo ethanoyl bromide (10). The spectral study of IR, 1D-NMR, and EI-MS corroborated the synthesized compounds. Methyl phenyl and methyl phenyl-substituted derivatives 12d and 12m with IC50 = 0.73 ± 0.54; 36.74 ± 1.24; 19.35 ± 1.28; 0.017 ± 0.53; and 0.038 ± 0.50 µM are found to be the most potent AChE, α-glucosidase, urease, and BChE inhibitors. The high inhibition potential of synthesized molecules against AChE, α-glucosidase, urease, and BChEenzymes inferred their role in enzyme inhibition properties.

Beliefs about the factors that motivate prosocial sentiments among people in the privileged class of Pakistan during the COVID-19 pandemic.

Drawing upon the theories of empathy-altruism and planned behavior, this study investigated beliefs about the factors that motivate prosocial sentiments among people in the privileged class of Pakistan during the COVID-19 pandemic. In-depth interviews were conducted with 31 participants who were deemed to be members of the privileged class within the class system of Pakistan. The results revealed nine themes including social interaction, peer influence, role models, collectivism, vicarious emotions, religiosity, capability, volition, and education.

Palisade Cartilage Tympanoplasty, an Alternative Surgical Approach for CSOM.

Introduction: The hearing outcome and graft take in patients of CSOM with sclerotic mastoids were studied using the novel technique of palisade cartilage tympanoplasty. Besides, it was compared with tympanoplasty type-1 above and over the cortical mastoidectomy in both groups. Materials and Methods: Out of 313 patients of CSOM, 125 had sclerotic mastoid and were included in the study. Palisade cartilage group patients were subjected to palisade cartilage tympanoplasty type-1. While as in the Temporalis fascia group patients, type-1 tympanoplasty was done using temporalis fascia as graft material. These procedures were performed in addition to cortical mastoidectomy done in all cases. Results: Statistically significant (P<0.001) mean postoperative hearing gain was achieved (> 20 dB) in both the groups with a reduction of AB gap to 13.3 & 11.79 dB, respectively. However, the post-surgery hearing outcomes achieved were similar in both groups (P=0.09). The overall graft take rate of 86% was seen in the Palisade cartilage group. The remaining 14% had graft take failure. The primary graft failure rate was 10% (5/50), and the secondary failure rate within six months of follow-up was 4% (2/50). The Temporalis fascia group graft take rate was higher (92%) than the Palisade cartilage group, with only 4 % (3/75) of cases having a primary graft failure rate. However, these findings (92% vs. 86%) were not statistically significant (P=0.2830). Conclusions: As the hearing outcomes and graft take rates were comparable in the two groups, the present study highlighted the use of palisade cartilage tympanoplasty in patients of CSOM with sclerotic mastoids as an alternative method to tympanoplasty.

Determination of antioxidant and bimolecular protective effect of Berberis calliobotrys Aitch. ex Koehne extracts and essential oil against H2O2 induced oxidative damage to pBR 322 DNA and RBCs.

We investigated the protective effect of fractions and essential oil from Berberis calliobotrys on H2O2 induced oxidative damage on pBR322 DNA. The crude plant material was extracted using 90% methanolic and liquid-liquid fractionation was accomplished. The essential oil analysis was performed using GC/MS. The FRAP and DPPH assays were performed to determine antioxidant activity. The DNA protection assay was performed using plasmid pBR 322 DNA. The essential oil analysis indicated presence of germacrene D (9.26%), stearic acid (7.50%), methyl tetradecanoate (6.36%) α-thujene (5.71%) and α-muurolol (5.30%) methyl eugenol (5.17%). In vitro analysis showed significant antioxidant activity of all tested extracts and essential oil. The extract showed significant effects at (1000 µg/mL) on pBR322 DNA. Finally it was concluded that Berberis calliobotrys possesses signifgant protective on effects pBR322 DNA and RBC cellular membrane.

Analysis of the efficacy of the pectoralis major myocutaneous flap in reconstructive head and neck surgery.

INTRODUCTION: Although free flaps have been used predominantly in past decades for the soft tissue reconstruction of head and neck malignancies, Pectoralis major myocutaneous flap (PMMF) is still a reliable workhorse for patients with co-existing co-morbidities or low economic status where free flaps are not feasible. PATIENTS AND METHODS: It was a retrospective study done on 36 patients of head and neck malignancies over the period of 5 years in which PMMF was used as a method of reconstruction in our hospital. Patients were followed up for a period of one year and outcome of PMMF was evaluated. RESULTS: Out of 36 patients 31 were of oral cancer and 5 were of carcinoma hypopharynx. Incidence of total flap necrosis was nil and partial flap necrosis was 16.6%. Orocutaneous fistula was found in 16.6%, wound dehiscence was in 19.4% and infection was found in 13.5% of patients. Non-flap related complications were found in 13.8% of patients. 35 out of 36 patients (97.2%) eventually achieved satisfactory surgical outcome of PMMF reconstruction. CONCLUSION: PMMF is a reliable method of reconstruction for head and neck malignancies especially in basic healthcare settings. With minimal expertise and groundwork, it is still a cost-effective workhorse flap for head and neck reconstruction.

Gas chromatographic-mass spectrometric analysis, antioxidant, antiproliferative and antibacterial activities of the essential oil of Prangospabularia.

The essential oil composition of the shoot parts of Prangos pabularia, growing in Drass area of Ladakh, India, along with its antioxidant, antibacterial and anticancer activity, is reported for the first time. Gas chromatography coupled with mass spectrometry (GC-MS) revealed the presence of 31 constituents, representing 97.342% of the total essential oil. The major constituents of essential oil were Durylaldehyde (62.161%), Bicyclo [3.1.1] hept-2-en-4-ol (8.846%), Chrysanthenyl acetate (5.120%) followed by unknown (3.420%), (-)-Spathulenol (3.028%), Mesityl aldehyde (2.402%) and Hexahydro farnesyl acetone (1.683%. Cytotoxic activity of the essential oil by MTT assay against human breast adenocarcinoma (MCF7), human breast (HBL-100), human cervical cancer (HELA) and human lung adenocarcinoma epithelial (A549) cells, at four different concentrations (20, 30, 50 & 100 µg/mL) revealed that the activity of 56.12% against A549 (human lung) cell line at 20 µg/mL concentration was the highest. The Essential oil displayed a significant free radical scavenging activity with DPPH. Antibacterial activity was carried out against 3 g positive and 2-g negative bacteria at four different concentrations using Agar Well Diffusion Method taking streptomycin sulphate as reference. The essential oil displayed significant and broad-spectrum antibacterial activity against different bacteria used. The MIC of the oil ranged from 2.06 to 5.00 µg/mL. The zones of inhibition were lesser for Micrococcus and Escherichia coli compared to other strains of bacteria.

Frequency of De Novo Hepatocellular Carcinoma after Direct-acting Antiviral Therapy for Chronic Hepatitis C: A Prospective Follow-up.

Background: Chronic hepatitis C (CHC) management has changed tremendously after direct-acting antivirals (DAAs) availability. Sustained virological response (SVR) has improved significantly, but one of the major concerns is the chances of de novo hepatocellular carcinoma (HCC) development after DAAs. The objective of the study is to calculate the frequency of newly diagnosed cases of HCC after antiviral therapy for CHC in Pakistan. Materials and methods: This prospective, interventional research was conducted from June 2017 to September 2020. All patients after antiviral therapy for CHC were followed with an ultrasound abdomen and α-fetoprotein, six monthly. Multiphasic computed tomography (CT) of the abdomen was performed in suspected cases. For quantitative variables, the mean and standard deviations were calculated, whereas the qualitative variables were analyzed by frequencies and percentages. Results: Among 180 patients, 110 were men and 70 were women with a mean age of 45.52 ± 11.71 years. One hundred and twenty-six patients were noncirrhotic, 38 had compensated cirrhosis while 16 had decompensated cirrhosis. One hundred and sixty-four (91.11%) patients achieved SVR, of which 22 (12.22%) patients developed new HCC during follow-up. Compensated cirrhosis group had 10 patients, the decompensated group had 12 patients, and the noncirrhotic group had no new HCC cases. Among patients with the new HCC, 12 achieved SVR. Conclusion: The risk of the development of HCC after antiviral treatment is highly significant among patients with liver cirrhosis. So, a strict surveillance strategy should be adopted in every cirrhotic patient following treatment with DAA agents even if they achieve SVR. Clinical significance: Chances of developing HCC are still significantly high even after achieving SVR with DAAs in patients with liver cirrhosis.Patients with liver cirrhosis should be under surveillance for HCC even after achieving SVR after DAAs treatment. How to cite this article: Rasool S, Hanif S, Ahmad A, et al. Frequency of De Novo Hepatocellular Carcinoma after Direct-acting Antiviral Therapy for Chronic Hepatitis C: A Prospective Follow-up. Euroasian J Hepato-Gastroenterol 2022;12(2):73-76.

Synthesis, spectral analysis and biological evaluation of 2-{[(morpholin-4-yl)ethyl]thio}-5-phenyl/aryl-1,3,4-oxadiazole derivatives.

A series of new derivatives of 4-(2-chloroethyl)morpholine hydrochloride (5) were efficiently synthesized. Briefly, different aromatic organic acids (1a-f) were refluxed to acquire respective esters (2a-f) using conc. H2SO4 as catalyst. The esters were subjected to nucleophillic substitution by monohydrated hydrazine to acquire hydrazides (3a-f). The hydrazides were cyclized with CS2 in the presence of KOH to yield corresponding oxadiazoles (4a-f). Finally, the derivatives, 6a-f, were prepared by reacting oxadiazoles (4a-f) with 5 using NaH as activator. Structures of all the derivatives were elucidated through 1D-NMR EI-MS and IR spectral data. All these molecules were subjected to antibacterial and hemolytic activities and showed good antibacterial and hemolytic potential relative to the reference standards.

Analysis of the efficacy of the pectoralis major myocutaneous flap in reconstructive head and neck surgery.

INTRODUCTION: Although free flaps have been used predominantly in past decades for the soft tissue reconstruction of head and neck malignancies, Pectoralis major myocutaneous flap (PMMF) is still a reliable workhorse for patients with co-existing co-morbidities or low economic status where free flaps are not feasible. PATIENTS AND METHODS: It was a retrospective study done on 36 patients of head and neck malignancies over the period of 5 years in which PMMF was used as a method of reconstruction in our hospital. Patients were followed up for a period of one year and outcome of PMMF was evaluated. RESULTS: Out of 36 patients 31 were of oral cancer and 5 were of carcinoma hypopharynx. Incidence of total flap necrosis was nil and partial flap necrosis was 16.6%. Orocutaneous fistula was found in 16.6%, wound dehiscence was in 19.4% and infection was found in 13.5% of patients. Non-flap related complications were found in 13.8% of patients. 35 out of 36 patients (97.2%) eventually achieved satisfactory surgical outcome of PMMF reconstruction. CONCLUSION: PMMF is a reliable method of reconstruction for head and neck malignancies especially in basic healthcare settings. With minimal expertise and groundwork, it is still a cost-effective workhorse flap for head and neck reconstruction.

Synthesis, characterization, antibacterial, hemolytic and thrombolytic activity evaluation of 5-(3-chlorophenyl)-2-((N-(substituted)-2-acetamoyl)sulfanyl)-1,3,4-oxadiazole derivatives.

A novel series of 5-(3-Chlorophenyl)-2-((N-(substituted)-2-acetamoyl)sulfanyl)-1,3,4-oxadiazole derivatives was efficiently synthesized and screened for antibacterial, hemolytic and thrombolytic activities. The molecule 7c remained the best inhibitor of all selected bacterial strains and furthermore possessed very low toxicity, 8.52±0.31. Compound 7a 7b and 7f showed very good thrombolytic activity relative to Streptokinase employed as reference drug. In addition to low toxicity and moderately good thrombolytic activity, the synthesized compounds possessed excellent to moderate antibacterial activity, relative to ciprofloxacin. All compounds especially 7b and 7f can be consider for further clinical studies and might be helpful in synthesis of new drugs for treatment of cardiovascular diseases.

BSA Binding, molecular docking and in vitro biological screening of some new 1, 2, 4-triazole heterocycles bearing azinane nucleus.

A series of new compounds (5a-q), derived from 5-(1-(4-nitrophenylsulfonyl) piperidin-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol (3) were proficiently synthesized to evaluate their biological activities. 1-(4-Nitrophenylsulfonyl) piperidine-4-carbohydrazide (2) was refluxed with phenylisothiocyanate to yield an adduct which was cyclized to compound 3 by reflux reaction with 10 % potassium hydroxide. The targeted compounds 5a-q, were synthesized by stirring alkyl/aralkyl halides (4a-q) and compound 3 in a polar aprotic solvent. 1H-NMR, 13C-NMR, EI-MS and IR spectral techniques were employed to confirm the structures of all the synthesized compounds. The compounds were biologically evaluated for BSA binding studies followed by anti-bacterial, anti-inflammatory and acetylcholinesterase (AChE) activities. The active sites responsible for the best AChE inhibition were identified through molecular docking studies. Compound 5e bearing 4-chlorobenzyl moiety found most active antibacterial and anti-inflammatory agent among the synthesized compounds. The whole library of synthesized compounds except compounds 5d and 5f was found highly active for AChE inhibition and recommended for in vivo studies so that their therapeutic applications may come in utilization.

Report - Synthesis of new antibacterial agents encompassing tosyl, piperidine, propanamide and 1,3,4-oxadiazole functionalities.

A series of propanamide compounds 6a-l was derived by N-substitution reactions, encompassing tosyl, piperidine and 1,3,4-oxadiazole moieties. The intended array of compounds 6a-l was afforded by a series of five steps reaction scheme. 1-Tosylpiperidin-4-carboxylate (1) was synthesized by the reaction of tosyl chloride (a) with ethyl isonipecotate (b) under mild basic conditions. Compound 1 was subjected to nucleophillic substitution by hydrazine to synthesize 1-tosylpiperidin-4-carbohydrazide (2). The compound, 5-(1-tosylpiperidin-4-yl)-1,3,4-oxadiazole-2-thiol (3) was synthesized by intermolecular cyclization of compound 2 by CS2 under strong basic conditions. The target compounds, 6a-l, were finally synthesized from 3 by reacting with different electrophiles, 5a-l, in an aprotic polar solvent with sodium hydride as an activator. The different propanamoyl electrophiles, 5a-l, were synthesized by the reaction of different aromatic and aliphatic amines, 4a-l, with 3-bromopropionyl chloride under mild basic conditions. The structural elucidation was carried out using modern spectroscopic techniques including IR, 1H-NMR and EI-MS. The antibacterial potential of synthesized compounds was assessed against five bacterial strains. Compounds 6a, 6c, 6d, 6e and 6f were found to be potent antibacterial agents.

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.