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

One hundred priority questions for the development of sustainable food systems in sub-Saharan Africa

Sub-Saharan Africa is facing an expected doubling of human population and tripling of food demand over the next quarter century, posing a range of severe environmental, political, and socio-economic challenges. In some cases, key Sustainable Development Goals (SDGs) are in direct conflict, raising difficult policy and funding decisions, particularly in relation to trade-offs between food production, social inequality, and ecosystem health. In this study, we used a horizon-scanning approach to identify 100 practical or research-focused questions that, if answered, would have the greatest positive impact on addressing these trade-offs and ensuring future productivity and resilience of food-production systems across sub-Saharan Africa. Through direct canvassing of opinions, we obtained 1339 questions from 331 experts based in 55 countries. We then used online voting and participatory workshops to produce a final list of 100 questions divided into 12 thematic sections spanning topics from gender inequality to technological adoption and climate change. Using data on the background of respondents, we show that perspectives and priorities can vary, but they are largely consistent across different professional and geographical contexts. We hope these questions provide a template for establishing new research directions and prioritising funding decisions in sub-Saharan Africa

Comparative analysis of procoagulant and fibrinogenolytic activity of crude protease fractions of turmeric species

Ethnaopharmacologial relevance: Turmeric rhizome is a traditional herbal medicine, which has been widely used as a remedy to stop bleeding on fresh cuts and for wound healing by the rural and tribal population of India. Aim of the study: To validate scientific and therapeutic application of turmeric rhizomes to stop bleeding on fresh cuts and its role in wound healing process. Materials and methods: The water extracts of thoroughly scrubbed and washed turmeric rhizomes viz., Curcuma aromatica Salisb., Curcuma longa L, Curcuma caesia Roxb., Curcuma amada Roxb. and Curcuma zedoria (Christm.) Roscoe. were subjected to salting out and dialysis. The dialyzed crude enzyme fractions (CEFs) were assessed for proteolytic activity using casein as substrate and were also confirmed by caseinolytic zymography. Its coagulant activity and fibrinogenolytic activity were assessed using human citrated plasma and fibrinogen, respectively. The type of protease(s) in CEFs was confirmed by inhibition studies using specific protease inhibitors. Results: The CEFs of C aromatica, C longa and C caesia showed 1.89, 1.21 and 1.07 folds higher proteolytic activity, respectively, compared to papain. In contrast to these, C amada and C zedoria exhibited moderate proteolytic activity. CEFs showed low proteolytic activities compared to trypsin. The proteolytic activities of CEFs were confirmed by caseinolytic zymography. The CEFs of C aromatica, C longa and C. caesia showed complete hydrolysis of A alpha, B beta and gamma subunits of human fibrinogen, while C amada and C zedoria showed partial hydrolysis. The CEFs viz., C aromatica, C longa, C caesia, C amada and C zedoria exhibited strong procoagulant activity by reducing the human plasma clotting time from 172 s (Control) to 66 s, 84 s 88 s, 78 s and 90 s, respectively. The proteolytic activity of C aromatica, C. longa, C caesia and C amada was inhibited (> 82%) by PMSF, suggesting the possible presence of a serine protease(s). However, C zedoria showed significant inhibition (60%) against IAA and moderate inhibition (30%) against PMSF, indicating the presence of cysteine and serine protease(s). Conclusion: The CEFs of turmeric species exhibited strong procoagulant activity associated with fibrinogenolytic activity. This study provides the scientific credence to turmeric in its propensity to stop bleeding and wound healing process practiced by traditional Indian medicine. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Exploring a new serine protease from cucumis sativus l

Coagulation is an important physiological process in hemostasis which is activated by sequential action of proteases. This study aims to understand the involvement of aqueous fruit extract of Cucumis sativus L. (AqFEC) European burp less variety in blood coagulation cascade. AqFEC hydrolyzed casein in a dose-dependent manner. The presence of protease activity was further confirmed by casein zymography which revealed the possible presence of two high molecular weight protease(s). The proteolytic activity was inhibited only by phenyl methyl sulphonyl fluoride suggesting the presence of serine protease(s). In a dose-dependent manner, AqFEC also hydrolysed A alpha and B beta subunits of fibrinogen, whereas it failed to degrade the gamma subunit of fibrinogen even at a concentration as high as 100 mu g and incubation time up to 4 h. AqFEC reduced the clotting time of citrated plasma by 87.65 %. The protease and fibrinogenolytic activity of AqFEC suggests its possible role in stopping the bleeding and ensuing wound healing process

Synthesis, characterization and pharmacological evaluation of different 1,3,4-oxadiazole and acetamide derivatives of ethyl nipecotate

A new series of N-substituted derivatives of 2-[(5-{1-[(4-chlorophenyl)sulfonyl]-3-piperidinyl}-1,3,4-oxadiazol-2-yl)sulfanyl]acetamide (6a-w) has been designed and synthesized with multifunctional moieties. The synthesized compounds were evaluated for their antibacterial and anti-enzymatic potential supported by % hemolytic activity. The synthesized compound 5-(1-(4-chlorophenylsulfonyl)-3-piperidinyl)-1,3,4-oxadiazole-2-thiol (3) was stirred with synthesized electrophiles as N-aryl/alkyl/aralkyl-2-bromoacetamide (5a-w) in an aprotic solvent under basic conditions to acquire the target molecules, 6a-w. The spectral analytical techniques of IR, EI-MS, 1H NMR and 13C-NMR were utilized for structural elucidation of synthesized molecules. The antibacterial screening against certain bacterial strains of gram-negative and gram-positive bacteria rendered compound 6i as good inhibitor of gram-negative bacterial strains. The enzyme inhibition revealed low potential against lipoxygenase (LOX) enzyme. The hemolytic study provided valuable information about cytotoxic behavior of synthesized molecules. Keywords: 1,3,4-Oxadiazole, Acetamide, Antibacterial activity, Hemolytic activity, Lipoxygenase inhibitio