Design, synthesis, in silico studies, and antidiabetic activity of several sulfanilamide incorporated 2,3-disubstitut-ed thiazolidin-4-ones

A panel of 2,3-disubstituted thiazolidin-4-ones 4a-n was synthesised from Schiff bases 3a-n derived from sulfanilamide, by reaction with thioglycolic acid. The compounds were characterised by means of IR, NMR, and Mass spectral data. Compounds 4a-n were screened for DPPH scavenging assay and compounds 4e, 4h, 4i, and 4n exhibited moderate activity. Compounds 4e, 4h, and 4i were tested at 200 mg/kg and 4e at 50 mg/kg b.w. orally for antidiabetic activity in fructose induced diabetic rats. They exhibited significant antidiabetic activity compared to the control group. Pioglitazone was used as a standard drug. The tested compounds exhibited better and ignificant serum cholesterol lowering activity when compared with the control and standard groups. They also reduced the triglyceride level after the 21st day; however, it was insignificant when compared to the control group. Compound 4n displayed the highest binding energy when docked with PPAR-γ followed by compounds 4e, 4h, and 4i when compared to pioglitazone. The physicochemical, drug likeness and ADME properties of the title compounds were found to be satisfactory.

Se sintetizó un panel de tiazolidinas-4-onas 2,3-disustituidas 4a-n a partir de las bases de Schiff 3a-n derivadas de la sulfanilamida por reacción con ácido tioglicólico. Los compuestos se caracterizaron por IR, RMN y datos espectrales de masa. Los compuestos 4a-n se analizaron para DPPH y los compuestos 4e, 4h, 4i y 4n mostraron una actividad moderada. Los compuestos 4e, 4h y 4i se probaron a 200 mg/kg y 4e a 50 mg/kg b.w. oralmente para la actividad antidiabética en ratas diabéticas, inducida por fructosa. Los compuestos mostraron una actividad antidiabética muy significativa en comparación con el grupo control. La pioglitazona se utilizó como fármaco estándar. Los compuestos ensayados mostraron una mejor y significativa actividad reductora del colesterol sérico en comparación con los grupos control y estándar. Estos compuestos también redujeron el nivel de triglicéridos después del 21° día, aunque fue insignificante en comparación con el grupo control. El compuesto 4n mostró la mayor afinidad de unión cuando se acopló a PPAR-γ, seguido de 4e, 4h y 4i en comparación con la pioglitazona. Las propiedades fisicoquímicas, la similitud con el fármaco y las propiedades ADME de los compuestos fueron satisfactorias, lo que los convierte en útiles agentes antidiabéticos.

Um painel de 2,3-disubstituído thiazolidina-4-ones 4a-n foram sintetizados a partir de bases Schiff 3a-n derivado da sulfanilamida por reacção com ácido tioglicólico. Os compostos eram caracterizado por IR, NMR e dados espectrais de massa. Os compostos 4a-n foram rastreados para O ensaio DPPH de limpeza radical e os compostos 4e, 4h, 4i e 4n exibiram actividade moderada. Os compostos 4e, 4h e 4i foram testados a 200 mg/kg e 4e a 50 mg/kg de peso corporal por via oral para antidiabéticos. actividade em ratos diabéticos induzidos por frutose. Exibiram uma actividade antidiabética altamente significativa actividade em comparação com o controlo. A pioglitazona foi utilizada como droga padrão. Os compostos testados exibiu uma melhor e significativa actividade de redução do colesterol sérico quando comparado comde triglicéridos após o 21° dia; no entanto, foi insignificante quando comparado com o controlo. O composto 4n mostrou a maior afinidade de ligação quando acoplado com PPAR-γ seguido de 4e, 4h, 4i quando comparado com pioglitazona. O propriedades físico-químicas, de semelhança com drogas e ADME dos compostos do título de propriedade também foram encontrados paraser satisfatórios, tornando-os agentes antidiabéticos úteis.

3-[4-chlorophenyl]-[1, 2, 3] oxadiazol-3-ium-5-olate and its 4-formyl analog-Ultrasound assisted synthesis and in-vitro anticancer evaluation against human tumor cell lines

The title compound, 3-[4-chlorophenyl]-4-formyl-[1, 2, 3] oxadiazol-3-ium-5-olate 5 was synthesized under ultrasonication by formylation of 3-[4-chlorophenyl]-[1, 2, 3] oxadiazol-3-ium-5-olate 4 and characterized by spectral studies. The ultrasonic method of synthesis was found to be simple, ecofriendly, economical, reduces reaction time and gave good yield when compared with traditional methods of synthesis. Anticancer activity of the compounds were tested against 60 human tumor cell lines and compared with standard drug vincristine sulphate. Compound 5 was found to be active against CNS [SNB-75, %GI=46.71], renal [UO-31, %GI=31.52], non small cell lung [NCI-H522, %GI=25.65], leukemia [MOLT-4, %GI=23.02] human tumor cell lines whereas, compound 4 against breast [MDA-MB-231/ATCC, %GI=19.90, T-47D %GI=16.50, MCF-7 15.10] and ovarian [IGROV1 %GI=19.30, OVCAR-4 %GI=17.90] human tumor cell lines. Compound 5 showed higher cytotoxicity against NCI-H23 cells [non small lung cancer cell panel] as compared to standard drug vincristine sulphate. Further structural modification of these compounds may lead to potent anticancer activity

Retrospective study on cost distribution of antiretroviral therapy in a tertiary care hospital.

Background: Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV), which is an RNA virus. The first case of AIDS in human beings was reported in 1981, and now spread of HIV infection is alarmingly high with around 20 million deaths. The objective of the study was to determine the cost distribution of antiretroviral therapy among autoimmune deficiency syndrome (AIDS) patient attending the anti-retroviral therapy (ART) center of the tertiary care center. Methods: The objective of the study was to determine the cost distribution of antiretroviral therapy among AIDS patient attending the ART center of the tertiary care center. The study was retrospective, 20 patients included in different age groups and categories the cost incurred toward patients were divided under different heads: medication, laboratory diagnosis, transport, and miscellaneous costs. Results: It was found that major part of the cost is spent on drugs. The cost of transport and lab diagnosis varied based on age and stage of the disease. Miscellaneous costs were also high and were proportional to other costs. Conclusion: HIV infected population is more likely to have a lower socioeconomic status which has varied effect on the effectiveness of highly active ART. Some of the problems faced by them are access to health care, transport, economic instability, etc. all these factors have an impact on outcome of treatment. Overall it can be found that preventive measure than treating has better impact on quality of life.

Drug utilization study on antidiabetic medications at SIMS-Shimoga a tertiary care hospital.

Background: Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. DM is a leading cause of blindness, end stage renal disease, and nontraumatic lower extremity amputations. The objective of the study was to evaluate the drug utilization pattern of antidiabetic medications at a tertiary care hospital. Methods: Demographic details of the patient were noted. Evaluation of the written prescription was carried out according to the requirements in case record form followed by computerization of data and analysis. Results: DM was almost equal in male (51%) and females (49%), the risk of DM was high after 40 years of age. Out of all the case records and prescriptions reviewed it was found that 23% had Type 1 DM, and 77% had Type 2 DM. In 46.35% cases, there was a family history of DM while in 47.44% cases it was absent, 6% were unaware. The average number of drugs per prescription was 3.26±0.24 and antidiabetic drugs at 1.72±0.28. Insulin alone was prescribed in 25.54% cases. Single antidiabetic agents as lone drugs were seen in 39.05%; combined oral antidiabetic drugs accounted for 25.54% cases. The combination of insulin and oral antidiabetic agents were prescribed in 9.85% cases. Conclusion: Metformin was the oral hypoglycemic agents, which was the most frequent prescribed as was insulin and its analogs. These drugs being essential in the treatment of diabetic patients should be made available to patients all the time.

Analysis of usage of diuretics in medical intensive care unit of SIMS-Shimoga a tertiary care hospital.

Background: Patients are admitted in the intensive care unit (ICU) with a history of various acute and chronic clinical conditions associated with organ failures. Compared to the patients admitted in the general wards the mortality and morbidity are high in ICU patients. The patients in ICU are subjected to multiple drugs; diuretic agents are liberally and deliberately used in this setup despite the lack of evidence supporting their benefits. Methods: The main aim of the study was to know the extent of use of diuretics in the ICU set up, to categorize the use of diuretics in different clinical conditions and different classes of diuretics used. The study also tried to determine adverse events and outcome in critically ill patients. The study was a retrospective cross-sectional of 3 months duration conducted in all patients admitted in the medical ICU of the tertiary care center. The study mainly concentrated on the usage of diuretics and related aspects. Results: Loop diuretics (54.81%) composed the major class, thiazides (30.84%). Potassium sparing diuretics (7%) and osmotic diuretics (7%) and carbonic anhydrase inhibitors (1%) were the other class of diuretics. The classes of drugs used in ICU along with diuretics were antibiotics (30%), analgesics (9.5%), anti-inflammatory (6.36%), and drugs acting on blood (10.18%) of total drugs used in ICU. Antacids/ laxatives (7.3%) and antiemetic (4.8%), the rest of drugs (15%) of drugs used in ICU. Conclusion: In almost 95% of cases, the combination of other drugs along with diuretics was considered to be rational.

Genotoxic evaluation of ornidazole and secnidazole in albino mice: an experimental study.

Background: The present study was planned to explore the genotoxic potential of some commonly used antimicrobials like ornidazole and secnidazole in swiss albino mice. Methods: Therapeutic equivalent doses of ornidazole and secnidazole were given by intra peritoneal route. Single dose in individual groups of mice (n=5 in each) was administered for acute study. Doses were repeated every 24 hrs for 7 times in additional groups of mice (n=5 in each) for sub-acute study. Cyclophosphamide served as positive control while normal saline as negative control. After 24 hrs of single dose (acute study) and last dose of drug administration in sub-acute study, about 0.5 ml of blood was collected by retro orbital sinus for comet assay as described earlier (Rojas E et al, 1999) and later the mice were sacrificed to aspirate the femoral bone marrow for micronucleus test as described earlier by described by Schmid W (1975). In comet assay, the total comet length and head diameter was measured under microscope using ocular & stage micrometer to calculate comet tail length. In micronucleus assay, the stained bone marrow tissue smears were scored for the frequency of micronucleated polychromatic erythrocytes (MnPCE) and also the ratio between polychromatic erythrocytes (PCE) to normochromic erythrocytes (NCE) was obtained. Results: It was analyzed by one-way ANOVA followed by Dunnet’s multiple comparison tests. Significant (P< 0.01) increase in comet tail length and percentage of micronucleated polychromatic erythrocytes (% MnPCE) was observed in groups treated with single and multiple doses of Cyclophosphamide whereas ornidazole and secnidazole treated groups did not show any significant changes. Conclusions: The results indicate that Ornidazole and secnidazole are devoid of genotoxicity.

Evaluation of the wound healing effect of Jasminum grandiflorum by wound contraction studies and wound breaking strength.

Background: Wound is a common process leading to inflammation and healing process. Jasminum grandiflorum is a plant widely grown in Karnataka and is mention in ancient medical systems to promote healing. So the study was taken up to confirm the anti-inflammatory effect of the plant. Methods: Excision and incision wound models in albino rats were used to study the wound healing effect. It was mainly studied by the degree of epithelisation at various intervals and compared with control group. The strength of the wound was assessed by its wound breaking strength at the end. Results: It was found that jasmine extract increased the degree of epithelisation and thus promoting wound healing. It was also found that the wound breaking strength was more in the drug treated group compared to normal. Conclusions: Jasminum grandiflorum leaf extract is known to have wound healing property.

Evaluation of wound healing effect of Jasminum grandiflorum in albino rats by histopathological studies.

Background: Wound healing is an important process in regeneration of the lost tissue, it involves various steps. Varieties of substances are known to interact in the healing process, some of the plant products are found to be beneficial. Jasmine leaves are mentioned to have healing effect in ancient literature. Hence the study was carried out to evaluate the wound healing effect by assessing the histopathological parameters. Methods: The study was done in the albino rats which were divided into various groups. The histopathological parameters were studied at regular intervals. Results: It was found that jasmine paste improved the wound healing process at all the stages. Conclusion: Jasminum grandiflorum has wound healing effect in albino rats.

Thought control study of medical students in Shimoga Institute of Medical Sciences (SIMS).

Background: Thought is a mental process which occurs in the Neo-cortex of the Brain [Cerebral cortices] based on the background knowledge, perception of the event or the action and understanding influenced by the individual traits or personality. Individual thoughts differ from person to person, time to time, and the events in life. Mainly thought is interpreted or understood based on the behaviour or when the person explains about it. Thought process in the brain can be acknowledged by an individual to have acceptable behavioural norms in the society, but cannot be explained by patients with disorder of thought processes. The behaviour of these individuals is acknowledged as the thought of the individual. Abnormal thought process occurs in psychiatric conditions like Psychosis, Anxiety disorder, Post traumatic disorder, mood disorders in varied manners. It also has implications or influences of the hormonal status and age of the person. In this study we are evaluating the thought control in the teenagers. Methods: the study was carried out in the medical students of SIMS-Shimoga. It is a questionnaire based study using a thought control questionnaire (TCQ). Results: The results were studied in five domains namely Distraction, Social, Worrying, Punishment and Re-appraisal, were found to vary within the acceptable limits and comparable with earlier studies. Conclusion: The findings in this study reflect the positive approach, handling of the unwanted and distracting thoughts in the teenagers.

Evaluation of cost effectiveness and efficacy of commonly used different antacid gel preparations.

Background: Gastroesophageal reflux disease (GERD) is a common clinical condition in Indian population. Antacids, which are available as over the counter (OTC) are the commonly prescribed drugs for treatment of GERD. Antacids manufactured and marketed by various multinational and local companies are available in the market. There is need for evaluating the cost effectiveness and efficacy of these antacids as a matter of public concern. Hence the present study was conducted to evaluate the cost effectiveness and efficacy of the commonly prescribed antacid gel preparations. Methods: Seven different gel formulations of antacids manufactured by different companies were evaluated. Cost effectiveness was done by calculating the cost per ml of antacid and also by palatability test. Efficacy was evaluated based on acid neutralizing capacity (ANC) of antacid preparations. Results: The highest cost was 0.305 Rs. per ml and lowest was 0.135 Rs per ml. Palatability score was high at 26.80 and low at 23.85. The antacid with lowest ANC was 20.5 mEq and the highest was 26.5 mEq. Conclusion: Cost effectiveness studies are beneficial in improving the prescribing pattern. It will be a benefit for both doctor as well as patient.

Multicystic Variant of Calcifying Cystic Odontogenic Tumor Associated With Odontome - Report of A Case And Review.

Calcifying cystic odontogenic tumor is an uncommon odontogenic neoplasm which is included in the heterogenous group of lesions under a broader description of Ghost cell odontogenic tumors. All these lesions have the presence of ghost cells as a common feature. Calcifying cystic odontogenic tumor is a unique lesion with variable biologic behaviour and found to occur with other odontogenic tumours. We present a case of Calcifying cystic odontogenic tumor occurring in a 15 year old boy involving an unerupted permanent canine and premolar. The tumor was multicystic in nature and was associated with a complex odontome. This article also includes an update on nomenclature and classification of ghost cell odontogenic lesions.

Keratocystic Odontogenic Tumor - A Wolf In Sheep's Clothing.

Keratocystic odontogenic tumor or Odontogenic keratocyst is a benign but one of the most locally aggressive type of developmental odontogenic cyst. Due to its invasive abilities in the bone and its high recurrence rate, it shares features of a cyst or a neoplasm and continues to riddle clinicians and researchers. Clinical and radiological expertise lies in diagnosing such lesions which present themselves as a coincidental finding in a routine out patient department. We report an unusual occurrence of a Collateral Odontogenic Keratocyst between the roots of two mandibular molars.

Wildervanck syndrome (cervico-oculo-acoustic syndrome).

Wildervanck syndrome i.e. cervico (Klippel-Feil anomalad) -oculo (Duane-Stilling-Turk phenomenon with bilateral abducens palsy)-acoustic (deafness) is a rare syndrome. We report here 4 cases diagnosed as Wildervanck syndrome and analyse their findings. One patient had an an atrial septal defect. Such association of congenital heart disease with Wildervanck syndrome has not been reported previously.