Supplementary Issues: Reviews of books, journal, congress, other media Special issues, and Scientific news


Phytochemical Profiling, Antimicrobial and Cytotoxic Properties of Four Phlomis species

Marjan Nikan, Mahdieh Kurepaz-Mahmoodabadi, Najmeh Mokhber-Dezfuli, Azadeh Manayi

International Pharmacy Acta, Vol. 5 No. 2 (2022), 4 Farvardin 2022, Page 1

Chewing of the sticks has been recently recommended by World Health Organization (WHO) as effective accessories for oral health. Salvadora persica plays an important role in maintaining the integrity of the tooth structure. The purpose of the present study was to determine the effectiveness of Salvadora persica extract on saliva pH after acidic changes. Participants were asked to take part in three different days with one-week interval in our open label non-randomized clinical trial. The effects of aqueous ethanolic (80%) extract of fresh S. persica sticks, distilled water, and sucrose on pH of saliva were examined at some time points, immediately to 20 min. The obtained results showed that the pH of saliva was significantly increased following gargling the distilled water (p=0.007) and S. persica extract (p=0.000) compared to the control group. In addition, the pH of saliva in a group which applied mouthwash of S. persica was significantly increased compared to the distilled water (p=0.04). Application of S. persica extract as a mouthwash increased the pH of saliva after acidic changes. Therefore, it may be recommended as an alternative to increase pH of oral cavity for oral health improvement.

Synthesis of Novel Indole Chalcones as Potential Cytotoxic Agents

Negar Sheikhi, Yalda Maddah, Seyedeh Sara Mirfazli

International Pharmacy Acta, Vol. 5 No. 2 (2022), 4 Farvardin 2022, Page 2

Cancer is the second leading cause of death in the world and its incidence and mortality rates are ever-growing. Nowadays, the clinical use of conventional anticancer drugs like Taxanes and Vinca alkaloids have been limited due to their drug resistance and neurotoxic effects. Therefore, much more attention has been paid to the discovery of new antitumor agents. Indole and chalcone scaffolds are found in many naturally occurring compounds and recently their derivatives have received significant attention not only because of their simple structure and ease of production, but also their biological activities, including antioxidant, antimicrobial, anticancer and anti-inflammatory activities. In this work, we have designed and synthesized different indole chalcone derivatives as a new series of potential cytotoxic agents. Desired chalcones were synthesized via the reaction of different aromatic aldehydes, in basic condition, with chlorobenzyl-1H-indole derivative. All the synthesized compounds were characterized by 1HNMR, 13CNMR, LC-MS and IR spectral data. The target compounds were obtained by optimized condensation reaction between different aromatic aldehydes and desired ketone with good to excellent yields.

Enhanced Corneal Permeation of Pilocarpine Using Liposome Technology

Eskandar Moghimipour, Sahar Farrokhi, Anayatollah Salimi

International Pharmacy Acta, Vol. 5 No. 2 (2022), 4 Farvardin 2022, Page 3

A novel liposomal pilocarpine formulation as an ophthalmic drug delivery system has been designed to treat patients with glaucoma. The purpose of the present study was to formulate and evaluate liposomes loaded with pilocarpine and to evaluate permeation through rabbit cornea. Liposomes containing pilocarpine were prepared using thin film method. The quantities of soya lecithin and cholesterol were changed to enhance the encapsulation of the drug. The physicochemical properties of the prepared liposomes were evaluated according to their viscosity, pH, particle size, in vitro drug release, and transcorneal rabbit permeation. Dialysis membrane method was utilized to assess drug release profile. The results indicated that the mean particle sizes of liposomes were 120.5-212 nm and the pH and viscosity of formulations were in the range of 6.30-6.63 and 43.85-80.1 cps, respectively. According to the release study results, maximumally 60% of the drug released from liposomal formulations after 24 hours of the experiment. Also, the cumulative percentage of the drug permeated through rabbit cornea was differing from 3.86 to 14.9%. Irrespective from the composition and characteristics of the different liposomal formulations, they significantly increased the drug partitioning, permeability coefficient and flux of pilocarpine in rabbit cornea ex vivo model in comparison to control drug solution. The present study proved that any alteration in composition and nature of pilocarpine liposomal formulations may affect the drug permeability parameters through corneal membrane and also physico-chemical properties. It is probably due to the change in corneal structure in the presence of different liposomes composition.

The skin is one of the most important defenses against pathogens. It can also be a penetrate way by wounds, damages and diseases. Some compounds like polycaprolactone fibers, phenolic plant compounds and naringenin are considered in wound treatment due to their stimulating collagen production, less side effects and high efficiency, respectively. Combining nanofibers and phenolic compounds is noticed to accelerating wound treatment. Materials and methods Synthesizing nanofibers of polycaprolactone and polyethylene glycol 3:1 in ratio using electrospinning and confirming by scanning electron microscope and FTIR test was done to perform this project. Then the rate of releasing of 3.125% naringenin of synthesized nanofibers were investigated by UV-visable. The animal test was done by creating wound on the Wistar breed rat and measuring the wound area during the test for 14 days and analyzing the datas use of imageJ and spss softwares. The wound tissue was removed for the tissue studies on the 15th day. Test results showed that the increase in naringenin concentration along nanofibers reduces the releasing rate. Likewise, in animal studies, outcomes showed that wound treatment in the nanofibers group on 1st, 4th, 7th days has no noticeable differences compared with the control group, on 10th and 14th days the treatment was decreased significantly and on the 1st day there was no significant differences compared with the nanofibers group containing naringenin. On the 4th , 7th , 10th , and 14th days there was no significant difference in nanofibers group containing naringenin compared with control group, but on 1st ,7th ,10th ,and 14th days a noticeable increase in healing was observed.

Thymus, which includes around 215 species, is an important genus of the Lamiaceae family. It comprises several species that are native to Iran and can serve as valuable medicinal plants because of their biological and pharmacological properties. Indeed, it is commonly used by the local inhabitants as an expectorant, antiseptic, antispasmodic, carminative, antirheumatic, and diuretic. Furthermore, this plants antibacterial, antifungal, and antiviral characteristics have made it a global source of potential antimicrobial agents. Analysis of the compounds of this plant by gas chromatography reveals the main compounds as the following: thymol (55.6 %), γ-terpinene (16.7 %), geraniol (4.6 %), p-cymene (4.0 %), limonene (2.6 %) E-Caryophyllene (1.9 %) and α-Pinene (1.8 %). The aim of this study was to investigate the molecular binding of the main components of Thyme migricus with the trimmer of spike protein of Corona virus by the molecular docking method. According to the method, first, the PDB file of ten main constituents of Thymus migricus was extracted from the Chemspider database. Then, the PDB file of trimmer of spike protein was obtained from the rcsb site. In the next step, molecular binding analysis was performed for each compound using HDOCK online software. This study showed that although all of the analyzed compounds were able to bind to the coronavirus spike trimmer to some extent, Carvacrol exhibited the lowest docking energy and RMSD. To validate the genuine effectiveness of Thymus migricus compounds, more in vitro and in vivo researches are needed.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of inflammation and pain is often accompanied by adverse gastrointestinal and renal side effects. Their anti-inflammatory activity results from inflammation of cyclooxygenase (COX), which catalyzes bioconversion of arachidonic acid to prostaglandins. Nowadays, it is well established that there are at least two COX isozymes, COX-1 and COX-2. COX-1 is responsible for the physiological production of prostaglandins while COX-2 is responsible for the elevated production of prostaglandins during inflammation. Thus, selective inhibition of COX-2 over COX-1 is useful for the treatment of inflammation and inflammation associated disorders with reduced gastrointestinal toxicities compared to NSAIDs. The withdrawal of some diaryl heterocyclic selective COX-2 inhibitors due to the adverse cardiovascular side effects delineates the need to explore and evaluate a new structural ring template possessing COX inhibitory activity. Therefore, in this study, new methyl 1,2-diaryl-4-hydroxy-5-oxo -2,5-dihydro-1H-pyrrole-3-carboxylate derivatives were designed and synthesized based on the structure-activity relationship of selective COX-2 inhibitors. Target compounds were synthesized in two steps. In the first step, 4-(methylthio)benzaldehyde, arylamine derivatives, and dimethylacetylenedicarboxylate (DMAD) in the presence of para-toluene sulfonic acid (PTSA) were stirred in ethanol for 72 hours. After the completion of the reaction, the resulting product was filtered off and recrystallized with ethanol. In the second step, a solution of Oxone and water was added to a well-stirred solution of the resulting product and diethylamine in acetonitrile. After the completion of the reaction, the resulting precipitates were filtered off and recrystallized with ethanol. In this study, new derivatives of new methyl 1,2-diaryl-4-hydroxy-5-oxo -2,5-dihydro-1H-pyrrole-3-carboxylate were designed, synthesized, and purified. The structure of the synthesized compounds was confirmed by FT- IR, 1HNMR, and MASS. We designed and synthesized some new methyl 1,2-diaryl-4-hydroxy-5-oxo -2,5-dihydro-1H-pyrrole-3-carboxylate derivatives as selective COX-2 inhibitors. The structure of synthesized compounds was confirmed by FT- IR, 1HNMR, and MASS. The COX-2 inhibitory activity of these compounds is under investigation.

Design and Synthesis of Novel Diaryl Oxo Pyrrole Derivative as Selective COX-2 Inhibitors

Marjaneh Pazoki, Tannaz Zebardast, Salimeh Amidi

International Pharmacy Acta, Vol. 5 No. 2 (2022), 4 Farvardin 2022, Page 7

Inflammation is the initial defense response of the body cells and tissues to various stimuli such as pathogens, infections, irritation, chemicals, mechanical or thermal injuries.These symptoms are due to the release of some inflammatory mediators including prostaglandins (PGs). Non-steroidal anti-inflammatory drugs (NSAIDs), widely used for the treatment of pain, pyrexia, inflammation, rheumatoid arthritis and osteoarthritis, block biosynthesis of prostaglandins by inhibiting the different isoforms of cyclooxygenase enzyme (COX-1,2) . The range of activities of NSAIDs against COX-1 compared with COX-2 explains the variations in the side effects of NSAIDs at their anti-inflammatory doses. Drugs which have a high potency against COX-2 and a low COX-2/COX-1 activity ratio will have potent anti-inflammatory activity with few side effects on the stomach and kidney. The recent market withdrawal of some coxibs such as rofecoxib and valdecoxib due to their adverse cardiovascular side effects clearly delineates the need to develop alternative structures with COX-2 inhibitory activity. For this reason novel scaffolds with high selectivity for COX-2 inhibition need to be found and evaluated for their anti-inflammatory effects. Therefore in this study, novel diaryl oxo pyrrole derivatives were designed and synthesized based on the structure-activity relationship of selective COX-2 inhibitors. Target compounds were synthesized in two steps: In the first step, a solution of 4-(Methylthio)benzaldehyde, arylamine derivatives and dimethylacetylenedicarboxylate (DMAD) in the presence of para-toluenesulfonic acid (PTSA) as a catalyst, was stirred in ethanol for 72 hours. After the completion of the reaction, the resulting product was filtered off and recrystallized with ethanol. In the second step, the resulting precipitates and diethylamine were stirred in acetonitrile. Then a solution of Oxone and water was added to the mixture. After the completion of the reaction, the resulting precipitates were filtered off and recrystallized with ethanol. A series of novel diaryl oxo pyrrole derivatives were synthesized in good yields and the structure of the compounds was confirmed by FT- IR, 1HNMR and MASS spectroscopy. In this study new derivatives of diaryl oxo pyrrole was synthesized in two steps. Molecular structures of the synthesized compounds were confirmed by FT- IR, 1HNMR and MASS spectroscopy.

The non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly medications in the world. The mechanism of action of these drugs is the inhibition of cyclooxygenase (COX) enzyme, which catalyzes the first step of the biosynthesis of PGG2 from arachidonic acid. COX isozymes exist at least in two isoforms, COX-1 and COX-2.The constitutive COX-1 isozyme is found in plateletes, kidneys, and the gastrointestinal tract and is believed to be responsible for the maintenance of physiological functions such as gastro protection and vascular homeostasis. In contrast, the COX-2 enzyme is the inducible isoform that is produced by various cell types upon exposure to cytokines, mitogens, and endotoxins released during injury and therefore molecules that inhibit its enzymatic activity would be of therapeutic value. The gastrointestinal side effects associated with NSAIDs are due to the inhibition of gastroprotective PGs synthesized through the COX-1 pathway. Thus, selective inhibition of COX-2 over COX-1 is useful for the treatment of inflammation and inflammation-associated disorders with reduced gastrointestinal toxicities when compared with NSAIDs. The recent market withdrawal of some coxibs such as rofecoxib and valdecoxib due to their adverse cardiovascular side effects clearly delineates the need to develop alternative structures with COX-2 inhibitory activity. For this reason novel scaffolds with high selectivity for COX-2 inhibition need to be found and evaluated for their anti-inflammatory effects. As a result, in this study, new methyl4-hydroxy-1-alkyl-2-aryl 5-oxo 2,5-dihydropyrrole-3-carboxylate derivatives were designed and sythesized based on the structure-activity relationship of selective COX-2 inhibitors. A mixture of 4-methylthiobenzaldehyde, arylamine derivatives and para-toluene sulfonic acid (PTSA) as a catalyst in ethanol was stirred at room temperature for 1 hour until a white precipitate appeared. Then, dimethylacetylenedicarboxylate (DMAD) was added. The reaction was stirred at room temperature until a new precipitate appeared. Finally, the resulting precipitate was recrystallized with ethanol. In the next step, a solution of Oxone in water was added to a well-stirred solution of the resulting product and diethyamine as a catalyst in acetonitrile. After the completion of the reaction, the precipitates were filtered and recrystallized with ethanol. All the target compounds were synthesized in good to high yields and the chemical structures were confirmed by IR, 1HNMR and Mass spectra. A novel series of methyl4-hydroxy-1-alkyl-2-aryl 5-oxo 2,5-dihydropyrrole-3-carboxylate derivatives was designed and synthesized as selective COX-2 inhibitors in good yields. The target compounds were characterized via IR, 1HNMR and Mass spectroscopies. The COX-2 inhibitory activity of the target compouds is under investigation.