A series of novel 4-Benzyl-1,3-thiazole derivatives was synthesized by applying analogue-based drug design approach and they were screened for anti-inflammatory activity. Darbufelone (CI 1004) a dual COX/LOX inhibitor, served as a lead molecule for designing a molecular scaffold. The derivatives with the 1,3 thiazole molecular scaffold bearing a side chain at position-2 resembling that of Romazarit (Ro-31-3948) were synthesized. The substitution at the second position of thiazole scaffold consisted of either carbalkoxy amino or aryl amino side chain. The introduction of an NH linker at the second position was the bioisoteric approach to impart the metabolic stability to the carbalkoxy side chains in designed molecules so as to avoid the likelihood of generating toxic moieties, like in Romazarit, which was withdrawn due to its toxicity profile. An important outcome of this study is the optimization of the substitution at the second position of the thiazole scaffold in eliciting better biological activity. The biological activity exhibited by the two designed series were in the order of carbalkoxy amino series > phenyl amino series. Molecule RS31 had emerged to be best compound in the whole series, having the side chain -NH-(C = O)O-R which resemble to Romazerit with 1,3 thiazole scaffold and substituted phenyl carbonyl group at fifth position derived from the retro-analysis of Darbufelone. This novel three-point pharmacophore, which is necessarily evolved from a lead-based drug design strategy, has opened up new avenues in designing of molecules acting on more than one rate-limiting step along the inflammatory cascade.
1 April 2004 in International Journal of Pharmaceutics
In ethno medicinal practices, the traditional healers use the genus Curcuma for the treatment of various ailments but Curcuma caesia Roxb. is a very less known and almost untouched drug. The present work attempts to establish the necessary pharmocognostic standards for evaluating the plant material of C. caesia Roxb. Various parameters, such as morphology, microscopy, physicochemical constants, and phytochemical profiles of the entire parts of the plant were studied and the salient diagnostic features are documented. Major chemical constituents, extractive values, physicochemical constants, and other features are also been recorded.
The present study investigated the protective effects of Foeniculum vulgare (fennel) essential oil (FEO) against genotoxicity induced by cyclophosphamide (CP). Mice bone marrow chromosomal aberration (CA), micronucleus, and sperm abnormality assays were employed to measure genotoxicity and cytotoxicity, respectively. The activities of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) content in the liver were also investigated spectrophotometrically. Animals were administered two different doses of FEO (1 and 2 mL/kg) continuously for 3 days at intervals of 24 hours by the oral route before tissue sampling. The results showed that CP produced a significant increase in the average percentage of aberrant metaphases and CAs, excluding gap and micronuclei formation in polychromatic erythrocytes (PCEs), produced cytotoxicity in mouse bone marrow cells, and induced abnormal sperms in the male germ line. CP also markedly inhibited the activities of SOD, CAT, and GSH and increased MDA content. Pretreatments with FEO significantly inhibited the frequencies of aberrant metaphases, CAs, micronuclei formation, and cytotoxicity in mouse bone marrow cells induced by CP and also produced a significant reduction of abnormal sperm and antagonized the reduction of CP-induced SOD, CAT, and GSH activities and inhibited increased MDA content in the liver. FEO inhibits genotoxicity and oxidative stress induced by CP.
15 November 2011 in Drug Development and Industrial Pharmacy
The main purpose of this work is to formulate self-microemulsifying drug delivery system (SMEDDS) using smaller molecular oil with Atorvastatin calcium as a model drug. Solubility of the selected drug was accessed in oils and surfactants. Percent transmittance (%T) test study was performed to identify the efficient self-microemulsifying formulations. Those formulations which showed higher value for %T were evaluated for droplet size, polydispersity index, ζ potential, refractive index and cloud point measurement. Effect of drug loading on droplet size, increasing dilution in different media, thermodynamic stability and in vitro dissolution was performed to observe the performance of the selected formulation. Further cytotoxicity and permeation enhancement studies were carried out on Caco2 cell lines. Of all the oils accessed for drug solubility, Capmul MCM showed higher solubility capacity for Atorvastatin calcium. Capmul MCM was better microemulsified using combination of Tween 20 and Labrasol surfactant. Droplet size was as low as 86.93 nm with polydispersity index and ζ potential at 0.195 ± 0.011 and −7.27 ± 3.11 mV respectively. The selected undiluted formulation showed refractive index values ranging from 1.40 to 1.47 indicating the isotropicity of the formulation. The selected formulation was robust to dilution in different media and thermodynamically stable. Dissolution profile was enhanced for the selected drug as compared to marketed formulation with t85% and DE values at 10 min and 80.15 respectively. Also cytotoxicity measurement showed minimum effect with good permeation enhancing capacity. Thus our study demonstrates the use of smaller molecular oil (Capmul MCM) for developing self-microemulsifying drug delivery system for better in vitro and in vivo performance.
The emergence and global spread of COVID-19 has disrupted the traditional mechanisms of education throughout the world. Institutions of learning were caught unprepared and this jeopardised the face-to-face method of curriculum delivery and assessment. Teaching institutions have shifted to an asynchronous mode whilst attempting to preserve the principles of integrity, equity, inclusiveness, fairness, ethics, and safety. A framework of assessment that enables educators to utilise appropriate methods in measuring a student’s progress is crucial for the success of teaching and learning, especially in health education that demands high standards and comprises consistent scientific content. Within such a framework, this paper aims to present a narrative review of the currently utilised methods of assessment in health education and recommend selected modalities that could be administered in an asynchronous mode during the COVID-19 pandemic. Assessment methods such as open-ended short answer questions, problem-based questions, oral exams, and recorded objective structured clinical exams (OSCE) would be appropriate for use in an asynchronous environment to assess the knowledge and competence of health professional students during COVID-19. Fairness and integrity can be ensured by using technological tools such as video and audio recording surveillance.