Rational Design, Synthesis, in Vitro, and in Silico Studies of Chlorophenylquinazolin-4(3H)-One Containing Different Aryl Acetohydrazides as Tyrosinase Inhibitors.

Tyrosinase plays a pivotal role in the hyperpigmentation and enzymatic browning of fruit and vegetable. Therefore, tyrosinase inhibitors can be of interest in industries as depigmentation compounds as well as anti-browning agents. In the present study, a series of chlorophenylquinazolin-4(3H)-one derivative were rationally designed and synthesized. The formation of target compounds was confirmed by spectral characterization techniques such as IR, 1 H-NMR, 13 C-NMR, and elemental analysis. Among the synthesized derivatives, compound 8l was proved to be the most potent inhibitor with an IC50 value of 25.48±1.19 µM. Furthermore, the results of the molecular docking study showed that this compound fitted well in the active site of tyrosinase with the binding score of -10.72.

A new series of Schiff base derivatives bearing 1,2,3-triazole: Design, synthesis, molecular docking, and α-glucosidase inhibition.

A series of new Schiff bases bearing 1,2,3-triazole 12a-o was designed, synthesized, and evaluated as α-glucosidase inhibitors. All the synthesized compounds showed promising inhibition against α-glucosidase and were more potent than the standard drug acarbose. The kinetic study on the most potent compound 12n showed that this compound acted as a competitive α-glucosidase inhibitor. The docking study revealed that the synthesized compounds interacted with the important residues in the active site of α-glucosidase.

In vitro and in vivo investigation of a novel amniotic-based chitosan dressing for wound healing.

It is more than a decade that amniotic membrane has been used as a wound dressing because of its anti-inflammatory, anti-microbial, anti-fibrotic, anti-scarring properties, as well as its pain relieving and epithelialization promoting features. However, amniotic membrane had limited applications because it needs to suture in surgery, is highly fragile, firmly adhere to the wound and may cause bleeding and pain when changing the bandage. This study investigated the possibility of development of a novel amniotic-based chitosan gel dressing as a potential wound repair substrate with marked efficacy. In this experiment, amniotic gel prepared based on chitosan/PVP gel containing human amniotic membrane extract (AME-Gel) was investigated in terms of wound-healing efficacy and scar preventive effects in a rat burn model. The levels of re-epithelialization and dermal regeneration were examined by histological assessment using H&E and Masson's trichrome staining. Also, we clarified the mechanism of healing and cytokine-releasing activities of AME as well as its effect on epithelization, angiogenesis, and fibroblast growth and migration. Our results revealed that AME-Gel induces epidermal and dermal regeneration at a shorter time through formation of granulation tissue, enhancement of fibroblast proliferation, and improvement of blood capillary formation concomitant with developing collagen bundles. Therefore, AME-Gel could be considered a simple and easy to be used as a biological dressing for any type of superficial burn wounds, without any adverse effects.

Preparation of hydrogel embedded polymer-growth factor conjugated nanoparticles as a diabetic wound dressing.

CONTEXT: Growth factors act in an integrated manner to promote the wound-healing process. However, probably due to early inactivation of these molecules in the wound site, their topical administration scarcely leads to a significant improvement in chronic wound repair. OBJECTIVES: With the aim of identifying improved therapeutics, a sodium carboxymethyl chitosan-recombinant human epidermal growth factor conjugate (NaCMCh-rhEGF) was developed. It is believed that conjugation will protect rhEGF against proteolysis and will mediate rhEGF release by α-amylase. MATERIAL AND METHODS: As hydrogels possess most of the desirable characteristics of an ideal dressing, we used our previously described chitosan-based hydrogel as a carrier for NaCMCh-rhEGF nanoparticles to make a novel wound dressing system. To evaluate the biological activity of NaCMCh-rhEGF and free rhEGF, the proliferation of fibroblasts was measured using a colorimetric assay. Additionally the stability of conjugated and free rhEGF against proteases was estimated. RESULT AND DISCUSSION: In vitro results revealed that the conjugated form exhibited more stability against proteolysis and also preserved its biological activity. Furthermore, in vivo studies were performed using an excision wound model on diabetic rats. After 15 d, the wound area in NaCMCh-rhEGF-hydrogel dressing group was significantly smaller than other groups and showed histological parameters equal to positive wound control group. CONCLUSION: A polymer conjugated rhEGF was developed that was more stable against proteases and reserved the biological activity of the drug. This dressing appears to be a competent candidate for chronic wound healing.

Preparation of hydrogel embedded polymer-growth factor conjugated nanoparticles as a diabetic wound dressing.

CONTEXT: Growth factors act in an integrated manner to promote the wound-healing process. However, probably due to early inactivation of these molecules in the wound site, their topical administration scarcely leads to a significant improvement in chronic wound repair. OBJECTIVES: With the aim of identifying improved therapeutics, a sodium carboxymethyl chitosan-recombinant human epidermal growth factor conjugate (NaCMCh-rhEGF) was developed. It is believed that conjugation will protect rhEGF against proteolysis and will mediate rhEGF release by α-amylase. MATERIAL AND METHODS: As hydrogels possess most of the desirable characteristics of an ideal dressing, we used our previously described chitosan-based hydrogel as a carrier for NaCMCh-rhEGF nanoparticles to make a novel wound dressing system. To evaluate the biological activity of NaCMCh-rhEGF and free rhEGF, the proliferation of fibroblasts was measured using a colorimetric assay. Additionally the stability of conjugated and free rhEGF against proteases was estimated. RESULT AND DISCUSSION: In vitro results revealed that the conjugated form exhibited more stability against proteolysis and also preserved its biological activity. Furthermore, in vivo studies were performed using an excision wound model on diabetic rats. After 15 d, the wound area in NaCMCh-rhEGF-hydrogel dressing group was significantly smaller than other groups and showed histological parameters equal to positive wound control group. CONCLUSION: A polymer conjugated rhEGF was developed that was more stable against proteases and reserved the biological activity of the drug. This dressing appears to be a competent candidate for chronic wound healing.

Cost-utility analysis of Macitentan Vs. Bosentan in pulmonary atrial hypertension.

OBJECTIVE: Endothelin (ET) receptor antagonists (ERAs) have considerable improvements in pulmonary arterial hypertension (PAH) patients' symptoms. Macitentan, a novel ERA, has more significant positive effects like reduction of morbidity and mortality in PAH patients by 45% and decreases PAH hospitalization. Besides, macitentan was able to improve both the physical and mental aspects of patients' lives. This study aimed to evaluate an incremental cost-utility analysis of macitentan compared with bosentan in PAH patients in the Iranian health care system. METHODS: We developed a hybrid model consisting of a decision tree in which PAH patients would take and continue either macitentan or bosentan with different probabilities. Subsequently, each patient would enter one of the 4 Markov's, each consisting of 5 states, PAH fraction I, PAH fraction II, PAH fraction III, PAH fraction IV, and death. The cycles and time horizon were considered 3 months and lifetime, respectively. We assessed the impact of each medicine on patients' quality-adjusted life-years (QALYs) and costs, consequently calculated the ICER (Incremental Cost-Effectiveness Ratio). The costs were measured in the dollar (1 dollar is equal to 42000 rials) with the perspective of the payer. The discount rates were assumed 3% for utility and 5% for costs. In addition, a sensitivity analysis was conducted. RESULTS: The costs are about 14163 dollars for bosentan and 13876 dollars for macitentan for each patient in a lifetime. The QALY produced per patient by macitentan was 0.81 more than that of bosentan. The calculated ICER was -357.47 which means that for each incremental QALY, the payer is charged less. CONCLUSION: Macitentan is preferable to and dominant over bosentan in both effectiveness and expenditure. Thus, the therapeutic regimen containing macitentan is introduced as a favorable treatment strategy.

Growth factor conjugation: strategies and applications.

Growth factors, first known for their essential role in the initiation of mitosis, are required for a variety of cellular processes and their localized delivery is considered as a rational approach in their therapeutic application to assure a safe and effective treatment while avoiding unwanted adverse effects. Noncovalent immobilization of growth factors as well as their covalent conjugation is amongst the most common strategies for localized delivery of growth factors. Today, immobilized and covalently conjugated growth factors are considered as a promising drug design and are widely used for protein reformulation and material design to cover the unwanted characteristics of growth factors as well as improving their functions. Selection of a suitable conjugation technique depends on the substrate chemistry and the availability of functional reactive groups in the structure of growth factor, the position of reactive groups in growth factor molecules and its relation with the receptor binding area, and the intention of creating either patterned or unpatterned conjugation. Various approaches for growth factor reformulation have been reported. This review provides an overview on chemical conjugation of growth factors and covers the relevant studies accomplished for bioconjugation of growth factors and their related application.

Fabrication and structure analysis of poly(lactide-co-glycolic acid)/silk fibroin hybrid scaffold for wound dressing applications.

Silk fibroin (SF) and poly(lactide-co-glycolic acid) (PLGA) have been proved to be invaluable polymers in the field wound healing. This study aims at optimizing the electrospinning process of those polymers to make a hybrid membrane as a chronic wounds dressing. After characterizing the scaffolds, PLGA/SF (2:1), and PLGA scaffolds were selected for further study according to their superior tensile mechanical properties. The attachment and proliferation of mouse fibroblasts (L929) on scaffolds were measured using colorimetric assay and scanning electron microscopy. Furthermore, to evaluate the wound healing effect of the scaffolds in comparison with gauze and Comfeel(®) dressings, an excision wound model was conducted on diabetic rats. On the postoperative days of 3, 6, 9, 12, and 15, residual wound area was calculated using macroscopic data. In vitro results showed that the attachment and proliferation of L929 were significantly increased on PLGA/SF (2:1) hybrid scaffold. Animal study and histopathological evaluation outcomes confirmed the in vitro results as well. On day 15, the residual wound area in PLGA/SF (2:1) hybrid membrane group was significantly smaller than PLGA and control groups. This promising scaffold has the potential to be used for the upcoming development of wound dressings with or without biological drugs.

Iranian pharmacists' knowledge, attitude and practice regarding counterfeit drugs.

Background Awareness of pharmacists about counterfeit drugs is necessary for health improvement in community. The purpose of the present study is to assess the knowledge and measure the professional attitude and practice of Iranian pharmacist about counterfeit drugs. In August 2008, a knowledge, attitude and practice (KAP) study was performed in a national sample of 794 pharmacists who participated in an Iranian Pharmacist Association congress. A questionnaire was prepared to collect Demographic and professional characteristics, Knowledge, attitude and practice of pharmacists regarding counterfeit drugs. The mean percent of participants who answer each practice questions correctly is 13.62% and none of questions have more than 14.7% of correct answer, while the participants' attitude towards the subject is at high level. None of demographic factors represented a significant relationship with knowledge and the only related parameters with attitude, were age and gender. Increasing age of pharmacists resulted in attitude improvement (p = 0.013) and women>s attitudes were better than men (p = 0.05).The only related parameters with practice, were the number of working hours per a week and attitude. Increasing the number of working hours per a week, resulted in decreasing the desirable practice (p = 0.041) and attitude also had a direct relationship with practice (p = 0.011). Conclusion The most important finding in the present study was the pharmacists> low knowledge and practice level about counterfeit drugs, while their attitude towards this subject was at a high level. The results point out the need for designing and implementing educational programs.