The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population.

The objective of this study is to estimate the prevalence of VKORC1, CYP2C9, and CYP4F2 genetic variants and their contribution to warfarin dose variability in Qataris. One hundred and fifty warfarin-treated Qatari patients on a stable dose and with a therapeutic INR for at least three consecutive clinic visits were recruited. Saliva samples were collected using Oragene DNA self-collection kit, followed by DNA purification and genotyping via TaqMan Real-Time-PCR assay. The population was stratified into derivation and validation cohorts for the dosing model. The minor allele frequency (MAF) of VKORC1 (-1639G>A) was A (0.47), while the MAF's for the CYP2C9*2 and *3 and CYP4F2*3 were T (0.12), C (0.04) and T (0.43), respectively. Carriers of at least one CYP2C9 decreased function allele (*2 or *3) required lower median (IQR) warfarin doses compared to noncarriers [24.5 (14.5) mg/week vs. 35 (21) mg/week, p < 0.001]. Similarly, carriers of each additional copy of (A) variant in VKORC1 (-1639G>A) led to reduction in warfarin dose requirement compared to noncarriers [21(7.5) vs. 31.5(18.7) vs. 43.7(15), p < 0.0001]. CYP4F2*3 polymorphism on the other hand was not associated with warfarin dose. Multivariate analysis on the derivation cohort (n = 104) showed that a dosing model consisting of hypertension (HTN), heart failure (HF), VKORC1 (-1639G>A), CYP2C9*2 & *3, and smoking could explain 39.2% of warfarin dose variability in Qataris (P < 0.001). In the validation cohort (n = 45), correlation between predicted and actual warfarin doses was moderate (Spearman's rho correlation coefficient = 0.711, p < 0.001). This study concluded that VKORC1 (-1639G>A), CYP2C9*2 & *3 are the most significant predictors of warfarin dose along with HTN, HF and smoking.

Imperatorin as a Promising Chemotherapeutic Agent Against Human Larynx Cancer and Rhabdomyosarcoma Cells.

Naturally occurring coumarins are bioactive compounds widely used in Asian traditional medicine. They have been shown to inhibit proliferation, induce apoptosis, and/or enhance the cytotoxicity of currently used drugs against a variety of cancer cell types. The aim of our study was to examine the antiproliferative activity of different linear furanocoumarins on human rhabdomyosarcoma, lung, and larynx cancer cell lines, and dissolve their cellular mechanism of action. The coumarins were isolated from fruits of Angelica archangelica L. or Pastinaca sativa L., and separated using high-performance counter-current chromatography (HPCCC). The identity and purity of isolated compounds were confirmed by HPLC-DAD and NMR analyses. Cell viability and toxicity assessments were performed by means of methylthiazolyldiphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, respectively. Induction of apoptosis and cell cycle progression were measured using flow cytometry analysis. qPCR method was applied to detect changes in gene expression. Linear furanocoumarins in a dose-dependent manner inhibited proliferation of cancer cells with diverse activity regarding compounds and cancer cell type specificity. Imperatorin (IMP) exhibited the most potent growth inhibitory effects against human rhabdomyosarcoma and larynx cancer cell lines owing to inhibition of the cell cycle progression connected with specific changes in gene expression, including CDKN1A. As there are no specific chemotherapy treatments dedicated to laryngeal squamous cell carcinoma and rhabdomyosarcoma, and IMP seems to be non-toxic for normal cells, our results could open a new direction in the search for effective anti-cancer agents.

Attitudes of pharmacy and nutrition students towards team-based care after first exposure to interprofessional education in Qatar.

Little is known regarding attitudes of healthcare professional students towards team-based care in the Middle East. As modernization of health systems is rapidly occurring across the Gulf Cooperation Council countries, it is important for students to engage in interprofessional education (IPE) activities. The objective of this study was to assess pre-clinical students' attitudes towards interprofessional healthcare teams after completion of their first IPE activity. A previously validated questionnaire was distributed to 25 pharmacy and 17 nutrition students at Qatar University after participation in an IPE event. Questions related to quality of team-based care and physician centricity. Results showed high agreement regarding high quality care provided by teams yet students were unsure of the value of team-based care when considering required time for implementation. Results provide baseline data for future studies to assess student attitudes throughout the professional programs and give valuable insight for future IPE program design in the Middle East.

Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study.

BACKGROUND: VKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans. METHODS: We did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged ≥18 years) who were taking a stable maintenance dose of warfarin were obtained at International Warfarin Pharmacogenetics Consortium (IWPC) sites and the University of Alabama at Birmingham (Birmingham, AL, USA). Patients enrolled at IWPC sites but who were not used for discovery made up the independent replication cohort. All participants were genotyped. We did a stepwise conditional analysis, conditioning first for VKORC1 -1639G→A, followed by the composite genotype of CYP2C9*2 and CYP2C9*3. We prespecified a genome-wide significance threshold of p<5×10(-8) in the discovery cohort and p<0·0038 in the replication cohort. FINDINGS: The discovery cohort contained 533 participants and the replication cohort 432 participants. After the prespecified conditioning in the discovery cohort, we identified an association between a novel single nucleotide polymorphism in the CYP2C cluster on chromosome 10 (rs12777823) and warfarin dose requirement that reached genome-wide significance (p=1·51×10(-8)). This association was confirmed in the replication cohort (p=5·04×10(-5)); analysis of the two cohorts together produced a p value of 4·5×10(-12). Individuals heterozygous for the rs12777823 A allele need a dose reduction of 6·92 mg/week and those homozygous 9·34 mg/week. Regression analysis showed that the inclusion of rs12777823 significantly improves warfarin dose variability explained by the IWPC dosing algorithm (21% relative improvement). INTERPRETATION: A novel CYP2C single nucleotide polymorphism exerts a clinically relevant effect on warfarin dose in African Americans, independent of CYP2C9*2 and CYP2C9*3. Incorporation of this variant into pharmacogenetic dosing algorithms could improve warfarin dose prediction in this population. FUNDING: National Institutes of Health, American Heart Association, Howard Hughes Medical Institute, Wisconsin Network for Health Research, and the Wellcome Trust.

Academic Entitlement Among Pharmacy Students in the Arab World: A Multi-National Exploratory Study.

OBJECTIVE: The study's aim was to explore academic entitlement among pharmacy students in different pharmacy colleges in the Arab World and assess associated factors. METHODS: This study design was a cross-sectional survey. Data were collected using a self-administered electronic questionnaire posted across pharmacy college networks in 10 Arab countries (Egypt, Iraq, Jordan, Lebanon, Libya, Oman, Palestine, Qatar, Saudi Arabia, and United Arab Emirates). The electronic survey was administered through Qualtrics Survey Software, and its link was open from January 23, 2022 to May 13, 2022. The multiple linear regression measured the association between different predictors and the academic entitlement. RESULTS: A total of 2386 surveys were received from students studying in 10 different Arab countries. The majority of responding students were male and studying in a Bachelor of pharmacy program. Students reported an agreeable attitude in 4 areas: rewards for efforts, customer orientation, customer service expectation, and general academic entitlement. In accommodation, a neutral attitude was reported, while they reported a disagreeing attitude in the responsibility avoidance domain. In grade haggling, the 3 items of the domain had different attitudes. Only 3 factors had a significant negative association with student entitlement (professionalism, GPA, and year in the study program). CONCLUSION: The academic entitlement scores among pharmacy students in the Arab World were high and had a negative association with professionalism perceptions. This study finding is a call for pharmacy programs to consider the effect of academic entitlement on pharmacy education and to obtain in-depth evidence on its magnitude and associated factors.

Differential binding of latrunculins to G-actin: a molecular dynamics study.

Latrunculins are unique macrolides containing a thiazolidinone moiety. Latrunculin A (1), latrunculin B (2), 16-epi-latrunculin B (3), and latrunculin T (4) were isolated from the Red Sea sponge Negombata magnifica. In the present study, after testing compounds 2-4 for cytotoxic activity, they were docked into the crystal structure of G-actin and subjected to binding energy calculation and a 20 ns MD simulation. The modeling study shows that latrunculins binding depends on both hydrophobic interaction of the macrocycle as well as H bonding of the thiazolidinone ring with Asp157 and Thr186. It was noticed that epimerization at C16 of latrunculin B was well tolerated as it could form an alternative H bonding network. However, opening of the macrocyclic ring deteriorates the actin binding due to reduced hydrophobicity. MD simulation showed that latrunculin B (2) possesses a more significant stabilizing effect on G-actin than latrunculin T (4) and could efficiently hinder the flattening transition of G-actin into F-actin. These findings could explain, at the molecular level, the impact of epimerization and macrolide ring-opening on latrunculins activity, an issue that has not been addressed before. Also, the study gives insights into the mechanism of cytotoxicity of diverse latrunculins and provides direction for future lead optimization studies.

Pharmacists' readiness and willingness to vaccinate the public in United Arab Emirates community pharmacies: A cross-sectional study.

Background: Pharmacist-administered vaccination is currently implemented in many countries worldwide. It has contributed to increased vaccine access and vaccine uptake. This observational cross-sectional study assessed community pharmacists' willingness, and readiness to administer vaccines to the public in the United Arab Emirates (UAE) and relate it to national and international policies on vaccination. Methods: This research was an online survey of 24-questions that was made available to community pharmacists via social media and WhatsApp. The survey was open for six weeks (from April to June 2022). Descriptive and inferential analysis was performed. Results: The questionnaire was completed by 374 of 575 (65%) respondents. More than half (64.2%) of the respondents agreed or strongly agreed that pharmacists should be able to vaccinate and 68.4% responded that they were willing to administer vaccines if local regulations allowed them to vaccinate. Most (81.8%) expressed willingness to complete training required to be able to administer vaccines in their pharmacies. Logistic regression showed that pharmacists defined as having high readiness were significantly more willing to undergo all essential training to start a vaccination service in their pharmacies than were pharmacists with poor readiness (OR 2.647; 95% CI: 1.518-4.615; p=0.001). High readiness was also significantly associated with agreement on safety of pharmacy-based vaccination (p=0.027). Conclusions: The majority of community pharmacists surveyed showed readiness to commence pharmacy-based vaccination services. Those with high readiness characteristics are amenable to receiving essential training and consider that vaccination in the community pharmacy setting would be safe.

Impact of an educational flyer and sensitization on performance-enhancement attitudes of bodybuilders in United Arab Emirates.

Background: A high proportion of bodybuilders use supplements to improve performance, with some turning to prohibited substances and methods. The attitudes of bodybuilders towards performance enhancement may be gauged through surveys such as the Performance Enhancement Attitude Scales (PEAS). Educational interventions are recommended as part of anti-doping measures. The objective of this project was to assess the impact of a pharmacy-led intervention using an antidoping educational flyer and the performance enhancement attitude scale to measure the attitude of bodybuilders in the United Arab Emirates (UAE). Methods: The PEAS eight-item short form questionnaire was administered to male bodybuilders in the UAE. The PEAS was conducted before and after administration of an educational flyer concerning the problems associated with supplement use among bodybuilders. The Wilcoxon Signed-Rank and Kruskal Wallis tests were used for data analysis. Results: A total of 218 bodybuilders, who reported taking dietary supplements, filled out the survey both pre and post viewing the antidoping educational flyer. A difference was observed between the full-time professional bodybuilders, students, and part-time bodybuilders with other primary occupations (p-value <0.05). In addition, PEAS score decreased among the study population for all eight PEAS items (p-value <0.05). Conclusions: The pharmacy-led intervention using an antidoping educational flyer and sensitization by PEAS achieved more favorable scores, suggesting a significant shift of opinion toward avoiding use of performance enhancing substances among the bodybuilder study population. More research is required on sustaining the attitude and demonstrating the impact on doping behavior.

CYP2C9 promoter variable number tandem repeat polymorphism regulates mRNA expression in human livers.

CYP2C9 is involved in metabolism of nearly 25% of clinically used drugs. Coding region polymorphisms CYP2C9*2 and *3 contribute to interperson variability in drug dosage and clinical outcomes, whereas the role of a regulatory polymorphism remains uncertain. Measuring allelic RNA expression in 87 human liver samples, combined with genotyping, sequencing, and reporter gene assays, we identified a promoter variable number tandem repeat polymorphism (pVNTR) that fully accounted for allelic CYP2C9 mRNA expression differences. Present in three different variant forms [short (pVNTR-S), medium (pVNTR-M), and long (pVNTR-L)], only the pVNTR-S allele reduced the CYP2C9 mRNA level compared with the pVNTR-M (reference) allele. pVNTR-S is in linkage disequilibrium with *3, with linkage disequilibrium r(2) of 0.53 to 0.75 in different populations. In patients who were taking a maintenance dose of warfarin, the mean warfarin dose was associated with the copies of pVNTR-S (p = 0.0001). However, in multivariate regression models that included the CYP2C9*3, pVNTR-S was no longer a significant predictor of the warfarin dose (p = 0.60). These results indicate that although pVNTR-S reduced CYP2C9 mRNA expression, the in vivo effects of pVNTR-S on warfarin metabolism cannot be separated from the effects of *3. Therefore, it is not necessary to consider pVNTR-S as an additional biomarker for warfarin dosing. Larger clinical studies are needed to define whether the pVNTR-S has a minimal effect in vivo, or whether the effect attributed to *3 is really a combination of effects on expression by the pVNTR-S along with effects on catalytic activity from the nonsynonymous *3 variant.

Sarcophine-diol inhibits expression of COX-2, inhibits activity of cPLA2, enhances degradation of PLA2 and PLC(γ)1 and inhibits cell membrane permeability in mouse melanoma B16F10 cells.

Sarcophine-diol (SD) is a semi-synthetic derivative of sarcophine with a significant chemopreventive effect against non-melanoma skin cancer both in vitro and in vivo. Recently, we have studied the effect of SD on melanoma development using the mouse melanoma B16F10 cell line. In this study, our findings show that SD suppresses cell multiplication and diminishes membrane permeability for ethidium bromide (EB), a model marker used to measure cell permeability for Ca²âº ions. SD also decreases protein levels of COX-2, and increases degradation of phospholipases PLA2 and PLC(γ)1 and diminishes enzymatic activity of the Ca²âº-dependent cPLA2. This lower membrane permeability for Ca²âº-ions, associated with SD, is most likely due to the diminished content of lysophosphosphatidylcholine (lysoPC) within cell membranes caused by the effect of SD on PLA2. The decrease in diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3) due to inhibition of PLC(γ)1, leads to the downregulation of Ca²âº-dependent processes within the cell and also inhibits the formation of tumors. These findings support our previous data suggesting that SD may have significant potential in the treatment of melanoma.

Sarcophine-diol, a skin cancer chemopreventive agent, inhibits proliferation and stimulates apoptosis in mouse melanoma B16F10 cell line.

Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3) and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances cellular level of tumor suppressor protein 53 (p53) and stimulates cleavage of the nuclear poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B16F10 tumor cells.

Dose-response on the chemopreventive effects of sarcophine-diol on UVB-induced skin tumor development in SKH-1 hairless mice.

Sarcophine-diol (SD) is a lactone ring-opened analogue of sarcophine. It has shown chemopreventive effects on chemically-induced skin tumor development in female CD-1 mice, as well as in a UVB-induced skin tumor development model in hairless SKH-1 mice at a dose of 30 µg SD applied topically and 180 mJ/cm(2) UVB. The objective of this study was to determine the dose-response on the chemopreventive effects of SD on SKH-1 hairless mice when exposed to a UVB radiation dose of 30 mJ/cm(2). This UVB dose better represents chronic human skin exposure to sunlight leading to skin cancer than previous studies applying much higher UVB doses. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into five groups. The control group was topically treated with 200 µL of acetone (vehicle), and the SD treatment groups were topically treated with SD (30 µg, 45 µg, and 60 µg dissolved in 200 µL of acetone) 1 h before UVB radiation (30 mJ/cm(2)). The last group of animals received 60 µg SD/200 µL acetone without UVB exposure. These treatments were continued for 27 weeks. Tumor multiplicity and tumor volumes were recorded on a weekly basis for 27 weeks. Weight gain and any signs of toxicity were also closely monitored. Histological characteristics and the proliferating cell nuclear antigen (PCNA) were evaluated in the mice skin collected at the end of the experiment. The dose-response study proved a modest increase in chemopreventive effects with the increase in SD dose. SD reduced the number of cells positively stained with PCNA proliferation marker in mice skin. The study also showed that SD application without UVB exposure has no effect on the structure of skin. The results from this study suggest that broader range doses of SD are necessary to improve the chemopreventive effects.

Standard-Setting for Continuing Education Assessment of Select New Competencies.

INTRODUCTION: Completion of continuing education hours might not guarantee the achievement of new competencies. Influenza vaccination training was provided to pharmacists in the United Arab Emirates (UAE), who had no similar training in their pharmacy degree. The training was developed and conducted at Gulf Medical University, UAE. Influenza vaccine administration is not yet a privilege for pharmacists in the UAE. This study focuses on determining whether a defensible cut score for the influenza vaccination training multiple-choice questions examination is feasible. METHODS: Influenza vaccination training and assessment happened on the same day. The Angoff (modified), Beuk, and Hofstee methods were used for standard-setting. Six subject matter experts who were involved in developing and conducting the first influenza vaccination training in the UAE evaluated the cut score using the Angoff method with the Delphi technique. RESULTS: The criterion-based cut score was 34.23 of 46 questions, with mean 74% and SD 2.24. Inter-rater reliability was 0.92 with standard errors of judgment 0.29 (0.63%). DISCUSSION: The modified Angoff is a credible method to set cut scores, reassured with Beuk and Hofstee methods for assessment of influenza continuing education. It is feasible and perhaps essential to determine a formal cut score for the continuing education assessment of health professionals on select new competencies.

Genomewide association analysis of warfarin dose requirements in Middle Eastern and North African populations.

To date, there has been no genomewide association study (GWAS) from the Middle East and North African (MENA) region to identify genetic variants associated with warfarin dose variability using this approach. In this study, we aimed to conduct the first GWAS of warfarin dose requirements in patients from the MENA region. A total of 132 Qatari (discovery) and 50 Egyptians (replication) were genotyped using Illumina Multi-Ethnic Global BeadChip Array. A GWAS was performed on log-transformed weekly warfarin dose in the studied population, adjusting for clinical characteristics and ancestry. The genomewide signals from the discovery cohort were tested in the Egyptian cohort. A GWAS meta-analysis, including the Qatari and Egyptian cohorts, was also performed and the output from this analysis was used in a gene-based analysis. The discovery analysis in Qatari identified five genomewide single-nucleotide polymorphisms (SNPs) in chromosome 16. These signals were replicated in the Egyptian cohort. Combining the two data through a GWAS meta-analysis strengthened the association in chromosome 16 with VKORC1 rs9934438 being the lead genomewide signal (ß = -0.17, 6 × 10-15 ). Other SNPs were identified in chromosome 10 at a p value less than 1 × 10-5 . The genetic variants within VKORC1 rs9934438 and CYP2C9 rs4086116 explained 39% and 27% of the variability in the weekly warfarin dose requirement in the Qatari and Egyptians, respectively. This is the first GWAS of warfarin dose variability in the MENA region. It confirms the importance of VKORC1 and CYP2C9 variants in warfarin dose variability among patients from the MENA region.

Exploring job satisfaction among pharmacy professionals in the Arab world: a multi-country study.

OBJECTIVES: The study objectives were to (1) describe the characteristics of the pharmacy professionals and (2) explore the association between job satisfaction and factors, such as work control, work stress, workload and organization and professional commitments. METHODS: This study was a cross-sectional design. The survey items were mainly adapted from the US National Pharmacist Workforce Survey. An electronic (Qualtrics) questionnaire was posted on pharmacist social media in several Arab countries. The survey link was posted from 22 March 2021 to 1 May 2021. The multiple linear regression measured the association between 12 independent variables and pharmacist job satisfaction. KEY FINDINGS: A total of 2137 usable surveys were received from pharmacists (54.7% female) working in 18 Arabic countries. The job satisfaction rate varied among countries in the Arab world. The fields with the highest satisfaction average included pharmaceutical marketing, academia and the pharmaceutical industry. At the same time, pharmacists working in community pharmacy and Ministry of Health/administrative positions had the lowest satisfaction rates. Overall, pharmacist satisfaction was average (3.1 out of 5). The pharmacists had the lowest satisfaction averages with income and job expectations. The pharmacists with bachelor's degrees had significantly lower satisfaction than pharmacists with postgraduate degrees. Male pharmacists had significantly higher job satisfaction compared with female pharmacists. Workload and the feelings of organization and professional commitments had significant positive associations with job satisfaction. CONCLUSIONS: The pharmacy profession in Arabic countries faced several challenges that negatively impacted job satisfaction. Improving work environment, professional management, income and organization loyalty is necessary to enhance pharmacist job satisfaction.

Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients.

BACKGROUND AND OBJECTIVE: Warfarin is a commonly used oral anticoagulant with a narrow therapeutic index and various genetic and clinical factors that influence interpatient variability in dose requirements. This study investigated the impact of genetic and nongenetic factors on warfarin dose requirements in Egyptians. METHODS: DNA was extracted from 207 patients taking warfarin for more than 2 months and genotyped for VKORC1 (3673 G>A), CYP2C9 *2*3*4*5*8, CYP4F2 (V33M; rs2108622), APOE (rs429358, rs7412), and CALU(rs339097) gene polymorphisms. Linear regression modeling was conducted to identify the genetic and nongenetic factors that independently influence warfarin dose requirements. RESULTS: VKORC1 3673 AA or GA genotype (P<0.0001), one or two variant alleles of CYP2C9 gene (P=0.0004), APOE ε2 haplotype (P=0.01), and increasing age (P<0.0001) were all associated with lower warfarin dose, whereas smoking (P=0.025) and pulmonary embolism (P=0.0059) showed association with higher warfarin doses. These factors explained 31% of the warfarin dose variability. This is the first independent confirmation of the association of the CALU rs339097 variant with higher warfarin dose requirement, although inclusion of this single nucleotide polymorphism in the multiple regression model failed to achieve significance (P=0.066). CYP4F2 (V33M) polymorphism was not significant (P=0.314), despite its high frequency in the studied population (42%). CONCLUSION: The study shows that VKORC1, CYP2C9 polymorphisms, APOE ε2 variant, and several clinical/demographic variables are important determinants of warfarin dose requirements in Egyptian patients. The percentage of variability explained by these factors is lower than in those of European ancestry, but similar to the variability explained in Asians and African ancestry.

Bioactive marine metabolites derived from the Persian Gulf compared to the Red Sea: similar environments and wide gap in drug discovery.

Marine life has provided mankind with unique and extraordinary chemical structures and scaffolds with potent biological activities. Many organisms and secondary metabolites derived from fungi and symbionts are found to be more environmentally friendly to study than the marine corals per se. Marine symbionts such as Aspergillus sp., a fungus, which can be isolated and grown in the lab would be a potential and continuous source of bioactive natural compounds without affecting the marine environment. The Red Sea is known for its biodiversity and is well-studied in terms of its marine-derived bioactive metabolites. The harsh environmental conditions lead to the development of unique metabolic pathways. This, in turn, results in enhanced synthesis and release of toxic and bioactive chemicals. Interestingly, the Persian Gulf and the Gulf of Oman carry a variety of environmental stresses, some of which are similar to the Red Sea. When compared to the Red Sea, the Persian Gulf has been shown to be rich in marine fungi as well, and is, therefore, expected to contain elaborate and interesting bioactive compounds. Such compounds may or may not be similar to the ones isolated from the Red Sea environment. Astoundingly, there are a very limited number of studies on the bioactive portfolio of marine-derived metabolites from the Persian Gulf and the Gulf of Oman. In this perspective, we are looking at the Red Sea as a comparator marine environment and bioactive materials repertoire to provide a futuristic perspective on the potential of the understudied and possibly overlooked bioactive metabolites derived from the marine life of the Persian Gulf and the Gulf of Oman despite its proven biodiversity and harsher environmental stress.

Semisynthetic latrunculin B analogs: studies of actin docking support a proposed mechanism for latrunculin bioactivity.

Latrunculins are unique macrolides containing a thiazolidinone moiety. Latrunculins A, B and T and 16-epi-latrunculin B were isolated from the Red Sea sponge Negombata magnifica. N-Alkylated, O-methylated analogs of latrunculin B were synthesized and biological evaluation was performed for antifungal and antiprotozoal activity. The natural latrunculins showed significant bioactivity, while the semisynthetic analogs did not. Docking studies of these analogs into the X-ray crystal structure of G-actin showed that, in comparison with latrunculins A and B, N-alkylated latrunculins did not dock satisfactorily. This suggests that the analogs do not fit well into the active site of G-actin due to steric clashes and provides an explanation for the absence of bioactivity.

Chemopreventive effects of sarcophine-diol on ultraviolet B-induced skin tumor development in SKH-1 hairless mice.

Sarcophine-diol (SD), one of the structural modifications of sarcophine, has shown chemopreventive effects on 12-dimethylbenz(a)anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin tumor development in female CD-1 mice. The objective of this study was to determine the chemopreventive effects of SD on UVB-induced skin tumor development in hairless SKH-1 mice, a model more relevant to human skin cancer, and to determine the possible mechanisms of action. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into two groups having 27 mice in each group: control and SD treatment. The control group was topically treated with 100 microL acetone and SD treatment group was topically treated with SD (30 microg/100 microL in acetone) 1 hour before each UVB radiation for 32 weeks. Tumor counts were recorded on a weekly basis for 30 weeks. Effects of SD on the expression of caspases were investigated to elucidate the possible mechanism of action. The proteins from epidermal homogenates of experimental mice were used for SDS-PAGE and Western blotting using specific antibodies against caspase-3, caspase-8 and caspase-9 respectively. TUNEL assay was used for determining DNA fragmented apoptotic cells in situ. Results showed that at the end of experiment, tumor multiplicity in control and SD treatment groups was 25.8 and 16.5 tumors per mouse respectively. Furthermore, Topical treatment of SD induced DNA fragmented apoptotic cells by upgrading the expressions of cleaved caspase-3 and caspase-8. This study clearly suggested that SD could be an effective chemopreventive agent for UVB-induced skin cancer by inducing caspase dependent apoptosis.

HPLC method for the quantitative determination of sarcophine, a source of cembranoids with cancer chemopreventive activity.

An accurate, reproducible and sensitive method for the quantitative determination of sarcophine in the organic extract of the Red Sea soft coral Sarcophyton species was developed and validated. Sarcophine concentration was determined by RP HPLC using ODS column. The mobile phase was made up of 70% acetonitrile in deionized water and the pH was adjusted to 3.5 with phosphoric acid. The flow rate was 1.5ml/min and the detector was set to 220nm. The HPLC analysis of several Sarcophyton glaucum samples collected from different locations in the Red Sea revealed that Hurghada had the highest sarcophine concentration.