Synthesis and evaluation of the antibiotic-adjuvant activity of carbohydrate-based phosphoramidate derivatives.

Phosphoramidates are becoming increasingly recognized as molecular targets for therapeutic development. Their biological functions are significantly influenced by their inherent properties such as reactivity, as well as the P-N backbone which allows for structural diversity. In this study we report the synthesis of novel carbohydrate-based phosphoramidate derivatives via the Staudinger-phosphite reaction; along with an evaluation of their adjuvant activity in combination with popular antibiotics. Our targets involved variation in both the sugar residue as well as the identity of the phosphoramidate. Moderate to excellent yields of these derivatives were obtained. Notable adjuvant activity was observed with the halogenated phosphoramidates. For the fluorinated glucose derivative in particular, a remarkable 32-fold decrease in the MIC of Ampicillin was obtained against Methicillin-resistant S. aureus.

Synthesis and Bioactivity of a Cyclopolypeptide from Caribbean Marine Sponge.

Synthesis of a natural proline-rich cyclopolypeptide - rolloamide A was carried out by coupling of tri- and tetrapeptide units Boc-Phe-Pro-Val-OMe and Boc-Pro-Leu-Pro-Ile-OMe after proper deprotection at carboxyl and amino terminals using carbodiimide chemistry in alkaline environment followed by cyclization of linear heptapeptide segment in the presence of base. The structure of synthesized peptide was confirmed by spectral techniques including FTIR, 1H NMR, 13C NMR, MS analyses. Newly synthesized peptide was subjected to biological screening against pathogenic microbes and earthworms. Cyclopeptide 8 possessed promising activity against pathogenic fungi Candida albicans (ZOI: 24 mm, MIC: 6 µg/mL) and Gram-negative bacteria Pseudomonas aeruginosa (ZOI: 27 mm, MIC: 6 µg/mL) and Klebsiella pneumoniae (ZOI: 23 mm, MIC: 12.5 µg/mL), in comparison to reference drugs - griseofulvin (ZOI: 20 mm, MIC: 6 µg/mL) and ciprofloxacin (ZOI: 25 mm, MIC: 6 µg/mL/ZOI: 20 mm, MIC: 12.5 µg/mL). Also, newly synthesized heptacyclopeptide exhibited potent anthelmintic activity against earthworms Megascoplex konkanensis, Pontoscotex corethruses, and Eudrilus species (MPT/MDT ratio - 8.22-16.02/10.06-17.59 min), in comparison to standard drugs - mebendazole (MPT/MDT ratio - 10.52-18.02/12.57-19.49 min) and piperazine citrate (MPT/MDT ratio - 12.38-19.17/13.44-22.17 min).

Multistage extraction and purification of waste Sargassum natans to produce sodium alginate: An optimization approach.

Sargassum in the Caribbean region has affected the livelihood of several coastal communities due to the influx of large quantities of the seaweed in recent times. This article seeks to explore how waste Sargassum natans can be utilized to produce sodium alginate. The novelty in this research lies in the optimization process, whereby multistage extraction and precipitation were investigated over commonly used single stage processing, in an effort to maximize both yield and purity. The results showed that a maximum yield of 19% was observed after 1 stage, while the purity was 74% after 4 stages. In addition, optimization of the multistage precipitation process using the Global Optimization Toolbox in MATLAB R2017b provided a novel model which indicated that a compromise between the maximum purity and yield can be obtained at 3 stages; 71-74% and 12-16% respectively. Furthermore, characterization was done using FTIR and NMR, with results comparable to a commercial sodium alginate brand, giving absorption bands at 1610 cm-1 and 1395 cm-1 and an M/G ratio of 0.51 respectively.