Sandeep Maharaj

Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status

Peptides have gained increased interest as therapeutics during recent years. More than 60 peptide drugs have reached the market for the benefit of patients and several hundreds of novel therapeutic peptides are in preclinical and clinical development. The key contributor to this success is the potent and specific, yet safe, mode of action of peptides. Among the wide range of biologically-active peptides, naturally-occurring marine-derived cyclopolypeptides exhibit a broad range of unusual and potent pharmacological activities. Because of their size and complexity, proline-rich cyclic peptides (PRCPs) occupy a crucial chemical space in drug discovery that may provide useful scaffolds for modulating more challenging biological targets, such as protein-protein interactions and allosteric binding sites. Diverse pharmacological activities of natural cyclic peptides from marine sponges, tunicates and cyanobacteria have encouraged efforts to develop cyclic peptides with well-known synthetic methods, including solid-phase and solution-phase techniques of peptide synthesis. The present review highlights the natural resources, unique structural features and the most relevant biological properties of proline-rich peptides of marine-origin, focusing on the potential therapeutic role that the PRCPs may play as a promising source of new peptide-based novel drugs.

Knowledge, attitude and practice of B.Sc. Pharmacy students about antibiotics in Trinidad and Tobago

Objective: The aim of this study was to assess the knowledge, attitude and practice of B.Sc. Pharmacy students about usage and resistance of antibiotics in Trinidad and Tobago. Methods: This was a cross-sectional questionnaire-based study involving B.Sc. Pharmacy students. The questionnaire was divided into five components including Demographics data, knowledge about antibiotic use, attitude toward antibiotic use and resistance, self-antibiotic usage and possible causes of antibiotic resistance. Data were analyzed by employing Mann-Whitney and Chi-square tests using SPSS version 20. Findings: The response rate was 83.07%. The results showed good knowledge of antibiotic use among students. The overall attitude of pharmacy students was poor. About 75% of participants rarely use antibiotics, whereas self-decision was the major reason of antibiotic use (40.7%) and main source of information was retail pharmacist (42.6%). Common cold and flu is a major problem for which antibiotics were mainly utilized by pharmacy students (35.2%). Conclusion: The study showed good knowledge of pharmacy students regarding antibiotic usage. However, students′ attitude towards antibiotic use was poor. The study recommends future studies to be conducted with interventional design to improve knowledge and attitude of pharmacy students about antibiotic use and resistance.

First Total Synthesis and Biological Screening of a Proline-Rich Cyclopeptide from a Caribbean Marine Sponge.

A natural heptacyclopeptide, stylissamide G (7), previously isolated from the Bahamian marine sponge Stylissa caribica from the Caribbean Sea, was synthesized via coupling of the tetrapeptide l-phenylalanyl-l-prolyl-l-phenylalanyl-l-proline methyl ester with the tripeptide Boc-l-leucyl-l-isoleucyl-l-proline, followed by cyclization of the linear heptapeptide fragment. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FT-IR, 1H NMR, 13C NMR and mass spectrometry. Results of pharmacological activity studies indicated that the newly synthesized cycloheptapeptide displayed good anthelmintic potential against Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus eugeniea at 2 mg/mL and in addition, potent antifungal activity against pathogenic Candida albicans and dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL.

Neurolaena lobata L. promotes wound healing in Sprague Dawley rats.

Background: The leaves of the Neurolaena lobata (Asteraceae) plant are used to control diabetes and heal wounds and infections. Aim: The ethanolic extract of N. lobata leaf was evaluated for its ability to heal inflicted wounds in rats using the excision wound model. Materials and Methods: Animals were divided into three groups of six each. Test group animals were treated topically with an ethanolic extract of N. lobata (1:1 with petroleum jelly, 100 mg/kg/day). Standard and control group animals were treated with mupirocin and petroleum jelly, respectively. Treatment was given for 13 days and the wound area was measured on alternate days. Parameters of healing assessed were the rate of wound contraction, period of epithelialization and hydroxyproline content. Antimicrobial activity of the extract was observed against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. Results: Phytochemical analysis of the extract showed the presence of saponins, tannins, alkaloids and flavanoids. Extract-treated animals exhibited 87% reduction in the wound area over 13 days when compared with the control (78%) and standard (83%) groups (P < 0.05). A significant decrease in the epithelialization period was noticed with the extract-treated test group animals compared with the controls and the standard group animals (P < 0.008). The hydroxyproline content of the extract-treated animals was higher (230.5 ± 42.1) when evaluated against the control and (79.0 ± 32.2) and the standard (115.0 ± 44.5) groups (P < 0.05). Conclusion: Increase in the rate of wound contraction and hydroxyproline content with decrease in epithelialization time in extract-treated animals support further evaluation of N. lobata as a pharmacotherapy for wound healing.

Total Synthesis and Pharmacological Investigation of Cordyheptapeptide A

The present investigation reports the synthesis of a phenylalanine-rich N-methylated cyclopeptide, cordyheptapeptide A (8), previously isolated from the insect pathogenic fungus Cordyceps sp. BCC 1788, accomplished through the coupling of N-methylated tetrapeptide and tripeptide fragments followed by cyclization of the linear heptapeptide unit. Structure elucidation of the newly synthesized cyclopolypeptide was performed by means of FT-IR, 1H-NMR, 13C-NMR, and fast atom bombardment mass spectrometry (FABMS), and screened for its antibacterial, antidermatophytic, and cytotoxic potential. According to the antimicrobial activity results, the newly synthesized N-Methylated cyclopeptide exhibited potent antibacterial activity against Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal activity against dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL, in comparison to the reference drugs, gatifloxacin and griseofulvin. In addition, cyclopolypeptide 8 displayed suitable levels of cytotoxicity against Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma (EAC) cell lines.

Toward the Synthesis and Improved Biopotential of an N-methylated Analog of a Proline-Rich Cyclic Tetrapeptide from Marine Bacteria

An N-methylated analog of a marine bacteria-derived natural proline-rich tetracyclopeptide was synthesized by coupling the deprotected dipeptide fragments Boc-l-prolyl-l-N-methylleucine-OH and l-prolyl-l-N-methylphenylalanine-OMe. A coupling reaction was accomplished utilizing N,N′-Dicyclohexylcarbodidimde (DCC) and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC·HCl) as coupling agents and Triethylamine (TEA) or N-methylmorpholine (NMM) as the base in the presence of the racemization suppressing agent. This was followed by the cyclization of the linear tetrapeptide fragment under alkaline conditions. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FTIR (Fourier-transform infrared spectroscopy), 1H NMR (Nuclear magnetic resonance spectroscopy), 13C NMR, and mass spectrometry. From the bioactivity results, it was clear that the newly synthesized proline-rich tetracyclopeptide exhibited better anthelmintic potential against Megascoplex konkanensis, Pontoscotex corethruses, and Eudrilus eugeniae at a concentration of 2 mg/mL as well as improved antifungal activity against pathogenic dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL, as compared to non-methylated tetracyclopeptide. Moreover, N-methylated tetracyclopeptide displayed significant activity against pathogenic Candida albicans.

Pharmaceutical Policy in Trinidad and Tobago

This chapter describes the pharmaceutical policy landscape in Trinidad and Tobago. The Republic of Trinidad and Tobago is a twin-island democratic nation located off the north coast of Venezuela in the Caribbean. The country is experiencing an epidemiological transition with a decline in the incidence of communicable diseases, and increases in chronic, noncommunicable diseases. Therefore, it is critical that pharmaceutical polices are reflective of our new health realities.

Development of a sustainable access to medicine model in the Caribbean: a case study of the chronic disease assistance program

Background The Caribbean region is one where there is a marked increase in non-communicable diseases and at the same time there are significant financial constraints. This study seeks to develop a methodology for a sustainable supply chain mechanism for medicines which can be implemented in these countries. To develop this, the chronic disease assistance programme currently implemented in Trinidad and Tobago was assessed and a template was developed around this.

Significance of pharmaceutical excipients in prescribed medicines: a case report

Pharmaceutical excipients need careful observation as they play a significant role in treatment outcomes. It is imperative for a physician to collect complete patient profile before prescribing new medications for current treatment. We present a case report on the significance of pharmaceutical excipients in prescribed medicines.

Impact of chronic disease assistance program on the retail pharmacy sector: A retrospective study

Objective: To assess the impacts of chronic disease assistance program (CDAP) on economic parameters, human resource and pharmacy structure and pharmaceutical care on the retail industry in Trinidad and Tobago. Materials and Methods: A partially perceptual retrospective investigation was carried out in 60 pharmacies from all regions (North East, North West, Central and South) in Trinidad. Questionnaires were distributed to all pharmacists of the each pharmacies indicated above. The validated questionnaires were distributed, over a period of approximately 2 weeks. Pharmacists employed at each pharmacy were asked to complete the questionnaire which consisted of 11 questions based on the three aspects of investigation. A five-point Likert scale (1 = strongly disagree, 5 = strongly agree) was used. Information from the completed questionnaires was tabulated in Microsoft Excel and the respective percentages and proportions were generated. Results: From the 60 pharmacies, 61% (n=37) believed that there was a decrease in sale of original brands while more than half of the respondents [53% (n=32)] believed there was an increase in sale of generics. The 60% (n=36) respondents viewed that there was compromised dispensary sale of original brands while 65% (n=39) felt there was increased orders for generic drugs. Of the CDAP prescriptions, it was disclosed that there was an overall increase in CDAP prescriptions from the year 2005-2008. A medium-scale pharmacy disclosed 1801 prescriptions in 2005, 2265 prescriptions in 2006, 3002 prescriptions 2007 and 3344 prescriptions in 2008 with overall increase in each year. Conclusions: The implementation of CDAP can explain the phenomenal increase in sale of generics drugs and the decrease in the sale of brands. There is a need for such a program in the developing countries.