Synthesis of 5(S)-Methyl-L-Proline containing Peptidomimetic Compounds and their In-Vitro Evaluation for Dipeptidyl Peptidase-4 Inhibition

Background: Type 2 diabetes mellitus (T2DM), which is the epidemic of the 21st century, has affected millions of people worldwide. Traditional methods available for the treatment are associated with various side effects. Among the newer therapies, DPP-4 (Dipeptidyl peptidase-4) inhibition has been a promising therapy for the past decade with the scope of further development, especially in peptidomimetics. Objective: 5(S)-methyl-L-proline containing peptidomimetic compounds were designed in the previous work. The designed compounds were synthesized and characterized by spectral methods, such as mass spectrometry, 1H NMR, and 13C NMR (Nuclear magnetic resonance) spectroscopy. The purity of the final compounds was determined by high-performance liquid chromatography (HPLC). The synthesized compounds were in vitro evaluated for their DPP-4 inhibitory activity. Method: Compounds were peptide in nature and were synthesized using the conventional synthesis approach, where peptide synthesis was done using an acid-amine coupling reagent. They were evaluated through fluorimetric enzyme-based assay using a DPP-4 inhibitor screening kit. Moreover, the CLARIOstar microplate reader instrument was used to measure fluorescence. Results: 5(S)-methyl-L-proline containing 13 compounds were synthesized. All of them were characterized for structural integrity using spectral methods. They had HPLC purity of more than 95% and were evaluated for DPP-4 inhibition. Compounds 001, 007, 010, 011, 014, and 017 were found to have good inhibition than others. These compounds were further evaluated at different concentrations to develop a linear correlation coefficient (R2). Conclusion: Six compounds were found to have good DPP-4 inhibition, hence it further opens the possibility of developing DPP-4 inhibitor-containing 5(S)-methyl-L-proline.

One-Pot Fabrication Cellulose/Silica Composite Microcapsules and Their Application in Cotton Fabrics

Research on multi-functional fabrics is an inevitable trend in the future development of textile field. Nevertheless, the key to the development of multifunctional fabric is how to solve the problem of contradictory function combination and how to achieve the multifunctions. In this work, a novel multifunctional fabric based on cellulose/silica microcapsules was developed by using green, facile and economical methods. Owing to the loaded essence and hydrophobic coupling reagent and UV absorber modified silica of microcapsules, the coated fabric not only exhibited slow-release property of fragrance, but also had excellent superhydrophobicity and ultraviolet (UV) protection. Furthermore, multifunctional fabric also displayed the durable superhydrophobicity and UV protection even after chemically or mechanically damaged. The development of mulfunctional fabrics largely depends on the development of textile functional finishing agent and finishing technology. Therefore, it is very important to develop new functional micrcapsules or finishing agent.

Hyaluronic Acid Functionalization with Jeffamine® M2005: A Comparison of the Thermo-Responsiveness Properties of the Hydrogel Obtained through Two Different Synthesis Routes

Hyaluronic acid (HA) of different molar masses (respectively 38,000, 140,000 and 1,200,000 g.mol−1) have been functionalized with a commercial poly(etheramine), Jeffamine® M2005, in order to devise physical thermo-responsive hydrogels. Two routes have been studied, involving the use of either water for the first one or of N,N’-Dimethylformamide (DMF), a polar aprotic solvent, for the second one. In the case of the water route, the reaction was performed using a mixture of N-(3-Dimethylaminopropyl)-N’-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS) as coupling reagents. The reaction was optimized while making sure no free M2005 remained in the final material, leading to M2005 grafting degrees of about 4%, which enabled the formation of hydrogels by increasing the temperature. In the case of the organic solvent route, propylphosphonic anhydride T3P® was used as a coupling reagent in DMF, resulting in a M2005 grafting degree of around 8% with better thermo-responsive properties of HA-g-M2005 compared to those obtained when the reaction was performed in water. However, the reaction systematically led to covalent cross-linking in the case of the HA, with the highest starting molar masses resulting in a very different rheological behaviour and with higher gel strength retaining thermo-responsive behaviour but being only poorly soluble in water.

Synthesis of Substituted -N-(5-((7-Methyl-2-Oxo-2H-Chromen-4-yl)-Methyl)-1,3,4-Thiadiazol-2-yl)-Benzamide Derivatives Using TBTU As Coupling Agent And Their Evaluation For Anti Tubercular Activity

: Tuberculosis remains a highly infectious disease across the world. In the identification of new antitubercular agents, coumarin clubbed thiadiazole amides have been synthesized and evaluated for in vitro antitubercular activity. Due to the growing concern about chemicals and their impact on the environment, greener and faster reaction conditions needed to be incorporated. Therefore, we used TBTU as a coupling reagent for efficient and facile synthesis of substituted-N-(5-((7-methyl-2-oxo-2H-chromes-4-yl)-methyl)-1,3, 4 - thiadiazol-2-yl)-benzamide 4a-j with good yields up to 95% in mild reaction condition. All the synthesized compounds were evaluated in vitro for antitubercular activity against the H37Rv strain of M.Tuberculosis. Compounds 4c, 4f, and 4j were found active at 25 µg/mL against M. tb H37Rv. Electron withdrawing substituents present on aromatic side-chain showed promising anti-tubercular activity.

Synthesis of Pentapeptide FWKVV (Phe-Trp-Lys-Val-Val) and Its Activity as Antioxidants

Antioxidant pentapeptides are pentapeptide compounds that have antioxidant activity. One of the pentapeptide compounds that have antioxidant activity is FWKVV. FWKVV is a linear pentapeptide with the amino acid sequence phenylalanine-tryptophan-lysine-valine-valine, which was first isolated to hydrolyzate the muscle protein of Miiuy croaker (Miichthysmiiuy). In addition to isolation, FWKVV compounds can be produced by the peptide synthesis method because this method requires a shorter time than the isolation method from natural materials. Synthesis methods commonly used are solution-phase peptide synthesis and solid-phase peptide synthesis (SPPS). However, the SPSS method is more efficient because it does not require purification in every process. The purpose of this study was to synthesize FWKVV compounds using the SPPS method and test their antioxidant activity. FWKVV has been synthesized using the SPPS method with HBTU/HOBt coupling reagent and Fmoc protective group. The FWKVV crud produced was 148.8 mg and had antioxidant activity against DPPH radicals with an IC50 value of 4.2 mg/mL.

Towards the synthesis of photobactin: methodology and metal binding aspects

Siderophores are metal-typically iron-chelating compounds that have received countless attention in research, as they can play a role in medicine intended for drug delivery and iron overload treatment. The synthesis of Photobactin has been of interest as it has been previously isolated (<10 mg) from Photorhabdus luminescence and has not once been synthesized. This thesis examined the preparation of Photobactin using a multi-step approach: synthesizing two building blocks individually and coupling them together with an amide coupling reagent. Both building blocks were synthesized successfully. However, the deprotection of the ester group on one of the building blocks has been uncooperative, and therefore the total synthesis of Photobactin was not achieved. Moreover, DFT computation calculations were performed to study Photobactin binding properties with Fe3+. According to the results, iron (Fe3+) is likely to form a hexadentate (6-coordinate ligand) or a tetradentate (4-coordinate ligand) complex with Photobactin. Each of the compounds leading to Photobactin was characterized using 1H and 13C-NMR. Some compounds were characterized using elemental analysis and performing 2D-NMR (COSY, HMBC, and HSQC) to make final assignments.

Towards the synthesis of photobactin: methodology and metal binding aspects

Siderophores are metal-typically iron-chelating compounds that have received countless attention in research, as they can play a role in medicine intended for drug delivery and iron overload treatment. The synthesis of Photobactin has been of interest as it has been previously isolated (<10 mg) from Photorhabdus luminescence and has not once been synthesized. This thesis examined the preparation of Photobactin using a multi-step approach: synthesizing two building blocks individually and coupling them together with an amide coupling reagent. Both building blocks were synthesized successfully. However, the deprotection of the ester group on one of the building blocks has been uncooperative, and therefore the total synthesis of Photobactin was not achieved. Moreover, DFT computation calculations were performed to study Photobactin binding properties with Fe3+. According to the results, iron (Fe3+) is likely to form a hexadentate (6-coordinate ligand) or a tetradentate (4-coordinate ligand) complex with Photobactin. Each of the compounds leading to Photobactin was characterized using 1H and 13C-NMR. Some compounds were characterized using elemental analysis and performing 2D-NMR (COSY, HMBC, and HSQC) to make final assignments.