Open Access Original Research Article

Preparation, Docking, Antimicrobial and Cytotoxic Activities of 2-arylquinazolinones

Nasrin Rahmannejadi, Kamiar Zomorodian, Zahra Faghih, Zeinab Faghih, Soghra Khabnadideh

Journal of Pharmaceutical Research International, Page 1-11
DOI: 10.9734/JPRI/2017/38244

Aims: Recently the use of antifungal drugs in human medicine has been increased, especially with the advent of AIDS epidemic. The extensive use of antifungal drugs and their resistance against fungal infections have led to the discovery of new antimicrobial compounds. Despite the growing list of azole drugs, their clinical value has been limited by their relatively high risk of toxicity and the emergence of drug resistance. Also, chemotherapy for cancer is frequently limited by organ toxicities and emergence of drug resistance in tumor cells. So efforts have focused on the development of new, less toxic, and more effective antifungal and cytotoxic agents.

Study Design: Preparation of several 2-arylquinazolinones with both antifungal and cytotoxic activities.

Place and Duration of Study: Department of Medicinal Chemistry, Department of Medical Mycology and Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran, from October 2016 to September 2017.

Methodology: Several synthetic analogues of 2-arylquinazolinones have been developed aiming at drugs with high potency and diminished toxicity. Thus, 2-arylquinazolinones (1b-12b) are prepared according to literature. The antimicrobial activities of these compounds against different species of microorganisms including fungi, gram positive and gram negative bacteria are evaluated. Broth micro-dilution method as recommended by clinical and laboratory standard institute (CLSI) was used for this purpose. We also evaluated the cytotoxic activities of the compounds against three human cancer cell lines (MCF-7, A549 and SKOV3) using colorimetric MTT cytotoxic assay. The specific binding mode of synthetic 2-arylquinazolinones have been also indicated by molecular modelling studies to show the interactions and binding orientation of compounds to CYP51 active site.

Results: Compound 1b showed desirable activities against bacteria as well as yeasts and filaments fungi. Compounds 2b, 7b, 8b and 9b can inhibit the growth of different yeasts with acceptable MIC. The cytotoxic results showed compounds 7b, 8b, 9b and 10b had partial inhibitory effects on cancer cell lines in particular lung adenocarcinoma.

Conclusion: 2-arylquinazolinones are respectable candidate for further studies in biological research.

Open Access Original Research Article

Development and Validation of Green Spectrophotometric Methods for Simultaneous Determination of Paracetamol, Pamabrom and Pyrilamine Maleate in Bulk and Pharmaceutical Dosage Form

Fawzia I. Habib, Manal M. Fouad, Noha S. Rashed, Ebtesam S. Mahmoud

Journal of Pharmaceutical Research International, Page 1-11
DOI: 10.9734/JPRI/2017/38353

Four simple and accurate spectrophotometric methods were developed for the simultaneous determination of paracetamol, pamabrom and pyrilamine maleate. The first is a zero order spectrophotometric method used for the determination of pyrilamine maleate in presence of paracetamol and pamabrom in the range of 0.5‐60 μg/mL by measuring the absorbance at       306.8 nm where paracetamol and pamabrom exhibits zero reading. The other three methods; bivariate, dual wavelength and area under the curve methods were developed for the simultaneous determination of paracetamol, pamabrom in presence of pyrilamine maleate. Bivariate calibration algorithm involves the use of two selected wavelengths; 260 nm and 280 nm for the determination of the two studied drugs. For the dual wavelength, paracetamol shows equal absorbance at    212.87 and 220.0 nm, where the differences in absorbance were measured for the determination of PBM. Similarly, differences in absorbance at 264.23 nm and 292.28 nm were measured for determination of paracetamol. In the area under curve method; the area between 237.14 to   247.14 nm was used for determination of paracetamol and 273.6 to 283.6 nm for pamabrom. Beer’s law was obeyed in the concentration ranges of 1-30 μg mL-1 for paracetamol and pamabrom in all methods. LOD was calculated and ranges from 0.149-0.766 μg/mL, while LOQ was found to be in the range of 0.556-1.145 μg/mL. The proposed methods were successfully applied for the simultaneous determination of PCM, PBM and PAM in their pharmaceutical preparation without interference from additives present with mean recovery ranging from 98.99 to 101.44%. Statistical analysis of the results obtained by the proposed spectrophotometric methods compared with a reported method revealed no significant difference between the proposed and reported methods confirming accuracy and precision at 95% confidence limit.

Open Access Original Research Article

Wound Healing Property and Phytochemical Analysis of Zanthoxylum Species from Uganda

Ogwang Patrick Engeu, Angupale Jimmy Ronald, Oloro Joseph, Baruga Evariste

Journal of Pharmaceutical Research International, Page 1-9
DOI: 10.9734/JPRI/2017/36766

Aim: The study evaluated the efficacy and possible mechanism of the stem bark of Zanthoxylum species used by communities and herbalists for wound healing in South Western Uganda.

Study Design: Experimental controlled.

Place and Duration: Departments of Pharmacy, Pharmacology and Pharmaceutical Sciences, Faculty of Medicine, Mbarara University of Science and Technology. The study done between August 2016 and February 2017.

Methodology: Excision wounds were humanely made on the bark of healthy albino rats and then randomly divided into four groups i.e Group I (Zanthoxylum spp (Zanthoxylum species) water extract) n=9, Group 2 (control herbal drug) n=6, Group 3 (distilled water) n=9 and Group 4 (neomcycine antibiotic) n=3. Treatments were applied twice a day for 15 days. The wound areas determined at baseline (day 1), then at day 6 and day 15 for each of the animals in groups 1, 2 and 3. Percentage reduction in wound areas was determined on day 6 and 15 and statistically compared.  On day 7 the rats in group 4 and three rats randomly picked by a blinded laboratory technician from groups 1 and 3 were humanely sacrificed for histology examination of wound tissues. Phytochemical analysis of the water extract of Zanthoxylum spp and the effect of the various solvent on extract efficacy were also evaluated.

Results: The Plant Zanthoxylum spp water extract was found to significantly reduce wound areas better than distilled water on day 6 and 15, (55.93±2.845) Vs (35.06±3.508), p=0.0312 and (93.18±1.721) Vs (74.89±5.604), p=0.0097, and marginally better than  herbal control drug on day 6, ( 55.93±2.845)  Vs (39.55 ± 6.524), p=0.0799. Five previously known alkaloids were identified by HPLC and LC-MS methods in the plant species as possible active compounds in wound healing. No significant difference was observed in the effects of the solvents on the efficacy of Zanthoxylum species on wound healing.

Conclusion: Zanthoxylum species studied shows great potential for stimulation of collagen formation and promoting natural wound healing mechanisms and therefore offers an alternative for wound treatment.

Open Access Original Research Article

Effect of Different Storage Conditions on the Stability and Efficacy of Some Reconstituted Oral Antibiotic Suspensions Sold in Port Harcourt, Nigeria

C. N. Stanley, S. E. Igala

Journal of Pharmaceutical Research International, Page 1-10
DOI: 10.9734/JPRI/2017/38553

Antibiotics for pediatric use are commonly available as dry powders for reconstitution into oral suspensions. Once reconstituted, these oral suspensions should be refrigerated to preserve their potency and deliver optimal benefit to the patient. However, for reasons ranging from lack of refrigerator and irregular power supply to lack of information and ignorance, these storage instructions are not always adhered to resulting in varying degrees of degradation of the reconstituted product. In spite of these constraints, Pharmacists have to ensure that patients receive optimum benefit from whatever drug they dispense in the course of rendering pharmaceutical care. This study examined the stability of three frequently prescribed pediatric reconstituted Cefuroxime axetil, Amoxicillin-clavulanate potassium and Azithromycin oral suspensions under different storage conditions. The reconstituted suspensions were stored in three different conditions with temperature ranging from 2°C to 29°C over a period of 5 days. Samples were assayed periodically using a validated UV/Vis spectroscopic method. Percentage concentrations were within 90 ± 5% up to the fifth day at condition A (refrigerated at 2 - 8°c). Under condition C (submerging in water at room temperature) the suspensions were preserved for at least 3 days. However, under condition B (storing in a cupboard at room temperature), extensive degradation was observed. In both conditions B and C, concentrations had fallen below 80% by the fifth day due to extensive degradation that occurred. Reconstituted oral suspensions should be used within 5 days if refrigerated or within 3 days if submerged in water and stored at room temperature in the absence of better alternatives.

Open Access Review Article

Clinical Risk in Surrogacy: A Review of the Limitations, Awareness, and Assessment of Prenatal / Neonatal Complications

Hala Mohamed Alkhalidi

Journal of Pharmaceutical Research International, Page 1-8
DOI: 10.9734/JPRI/2017/38685

Infertility due to clinical complications or conditions arising due to congenital or acquired absence of a healthy functioning uterus in women leads the couple to opt for surrogacy that involves high risk both for mother and future child. In some societies as in India and in Eastern European countries, Surrogacy has turned as wealthy practice, badly influencing the young minds of couples whom are healthy to reproduce a child but do not want the pain and to waste the time. Many reports do not highlight the associated obstetric risks or warn about the extreme cautions that must be exercised while adopting surrogate pregnancies. In spite of international guidelines clinical practice that advice surrogacy, prepregnancy counseling helps the couple to realize the clinical implications and even in decision over surrogacy. Majority of the literature available are focused on treatment or addressing the use of surrogacy, a special focus on the drawbacks in surrogacy and how antenatal, intrapartum and postpartum care in surrogacy is vital are outlined. Also, there are no or limited data reported on the risk, complications and obstetric outcomes that are of greater significance in explaining the health issues, psychological and surrogacy effects on society. Therefore, in this review we focus on the assessing and outlining the possible risk, clinical complications that are reported due to surrogacy. We also expect this essay provides valuable insights and reasons for the individuals clearly indicating potential harm araised due to surrogacy and to limit or discourage the practice.