Synthesis of curcumin based imidazo[2,1-b]thiazole derivatives and their biological evaluation as antiproliferative agents

13-20Motivated by the antiproliferative potential of curcumin and imidazothiazoles, a series of curcumin based imidazo[2,1-b] thiazole derivatives have been prepared, characterized and evaluated for their anticancer activity against various human cancer cell lines. These synthesized compounds have been found to have appreciable to moderate activity. Consequently, compounds 8a and 8g display noteworthy cytotoxicity with IC50 values of 7.2 μM and 4.7 μM, respectively, against A549 cell line. Furthermore, compounds 8a, 8b and 8g exhibit substantial cytotoxicity with IC50 values ranging between 9.1 μM to 9.9 μM respectively, against HeLa cell line. Interestingly, compounds 8a and 8g exhibit appreciable cytotoxicity with IC50 values ranging between 7.5 μM to 8.7 μM respectively, against DU145 cancer cell line. Overall, four compunds (8a, 8b, 8g and 8h) demonstrate IC50 values less than 10 μM against selected human cancer cell lines. They could be taken further for investigation of their mode of action and other parameters

Synthesis and antimicrobial evaluation of benzothiazole linked isoxazole Schiff bases

1463-1470A new series of benzothiazole linked isoxazole Schiff base derivatives have been prepared and characterized by suitable spectroscopic methods via 1H and 13C NMR, ESI-MS and IR spectra. These compounds have been further screened for their antimicrobial activity against a panel of microorganisms. Among them, compounds 12d, 12g and 12l demonstrate promising antimicrobial activity against all the tested strains with MIC values ranging between 3.9 – 62.5 μg/mL. Further, compounds 12d, 12g and 12l exhibit promising antifungal activity with MIC values ranging between 7.8 – 32.5 μg/mL. Further studies are underway for determining the antifungal molecular mechanisms of these potential compounds

Synthesis and antimicrobial evaluation of benzothiazole linked isoxazole Schiff bases

A new series of benzothiazole linked isoxazole Schiff base derivatives have been prepared and characterized by suitable spectroscopic methods via 1H and 13C NMR, ESI-MS and IR spectra. These compounds have been further screened for their antimicrobial activity against a panel of microorganisms. Among them, compounds 12d, 12g and 12l demonstrate promising antimicrobial activity against all the tested strains with MIC values ranging between 3.9 – 62.5 µg/mL. Further, compounds 12d, 12g and 12l exhibit promising antifungal activity with MIC values ranging between 7.8 – 32.5 µg/mL. Further studies are underway for determining the antifungal molecular mechanisms of these potential compounds

Synthesis of curcumin based imidazo[2,1-b]thiazole derivatives and their biological evaluation as antiproliferative agents

Motivated by the antiproliferative potential of curcumin and imidazothiazoles, a series of curcumin based imidazo[2,1-b] thiazole derivatives have been prepared, characterized and evaluated for their anticancer activity against various human cancer cell lines. These synthesized compounds have been found to have appreciable to moderate activity. Consequently, compounds 8a and 8g display noteworthy cytotoxicity with IC50 values of 7.2 μM and 4.7 μM, respectively, against A549 cell line. Furthermore, compounds 8a, 8b and 8g exhibit substantial cytotoxicity with IC50 values ranging between 9.1 μM to 9.9 μM respectively, against HeLa cell line. Interestingly, compounds 8a and 8g exhibit appreciable cytotoxicity with IC50 values ranging between 7.5 μM to 8.7 μM respectively, against DU145 cancer cell line. Overall, four compunds (8a, 8b, 8g and 8h) demonstrate IC50 values less than 10 μM against selected human cancer cell lines. They could be taken further for investigation of their mode of action and other parameters

A concise and stereoselective synthesis of both enantiomers of altholactone and isoaltholactone

A concise and flexible stereoselective route to synthesize both enantiomers of the highly functionalized α,β-unsaturated-δ-lactones, altholactone and isoaltholactone, from readily available cinnamyl alcohol is described. This approach derived its asymmetry from Sharpless catalytic asymmetric epoxidation and Sharpless asymmetric dihydroxylation reactions. The resulting diols were produced in high enantiomeric excess and were cyclized in a stereoselective manner in the presence of a catalytic amount of camphor sulphonic acid. The synthesis of both enantiomers of altholactone and isoaltholactone has been achieved in a concise and highly enantioselective manner

Highly stereoselective synthesis of C-(alkynyl)-pseudoglycals from δ-hydroxy-α,β-unsaturated aldehydes

An efficient and novel methodology for the synthesis of C-(alkynyl)-pseudoglycals from δ-hydroxy-α,β-unsaturated aldehydes has been developed

[Bmim]BF<SUB>4</SUB> ionic liquid: a novel and recyclable reaction media for the synthesis of homoallylic amines

The imines derived in situ from aldehydes and amines undergo smoothly nucleophilic addition with allyltributylstannane in 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF<SUB>4</SUB>) ionic liquid to afford the corresponding homoallylic amines in high yields with high selectivity. The recovered ionic liquid can be recycled in four to five runs with gradual decrease in activity

IMPURITY PROFILING IMPURITY PROFILING OF THIAMINE HYDROCHLORIDE INJECTION BY RP-HPLC AND CHARACTERIZATION OF DEGRADATION PRODUCT BY LC-MS/MS/QTOF

Objective: To propose a comprehensive, simple, and affordable RP-HPLC method for impurity profiling and characterization of unknown degradation products of thiamine hydrochloride injectable formulation. Methods: The chromatographic separation employs gradient mode using the octadecyl silane column using a mobile phase consisting of phosphate buffer with ion pair reagent, acetonitrile, and methanol delivered flow rate at 1.2 ml/min. The detection was carried out at 248 nm using empower software. LC-MS/MS/QTOF hyphenated technique was used for isolation and characterization of unknown degradation impurity. The performance of the method was systematically validated as per ICH Q2 (R1) guidelines. Results: Degradation product observed in accelerated stability was characterized by LC-MS/MS/QTOF hyphenated technique and found m/z value 351.1604 and postulated as an oxidative degradation product of thiamine due to excipient interaction. The validated method was sensitive, selective, and specific data proves the method is precise and accurate from LOQ to 150% level and results are within 95-108% and less than 4.5% RSD. The developed method is linear from 0.03-58.83 µg/ml with a correlation coefficient of more than 0.990 and LOD and LOQ value ranged from 0.03&nbsp;to1.51&nbsp;μg/ml. Conclusion: An efficient RP-HPLC method for impurity profiling of thiamine injectable formulation was successfully developed and unknown degradation product observed instability condition samples characterized by LC-MS/MS/QTOF technique. The validated method can be successfully employed for the impurity profiling of thiamine injectable in the quality control department

A comparative study of two reconstructive methods and different recommendations in intracavitary brachytherapy

Purpose: Intracavitary brachytherapy (ICB) is a widely used technique in the treatment of cervical cancer. In our Institute, we use different reconstructive methods in the conventional planning procedure. The main aim of this study was to compare these methods using critical organ doses obtained in various treatment plans. There is a small difference in the recommendations in selecting bladder dose point between ICRU (International Commission on Radiation Units & Measurements) -38 and ABS (American Brachytherapy Society). The second objective of the study was to find the difference in bladder dose using both recommendations.Material and methods: We have selected two methods: variable angle method (M1) and orthogonal method (M2). Two orthogonal sets of radiographs were taken into consideration using conventional simulator. All four radiographs were used in M1 and only two radiographs were used in M2. Bladder and rectum doses were calculated using ICRU-38 recommendations. For maximum bladder dose reference point as per the ABS recommendation, 4 to 5 reference points were marked on Foley’s balloon.Results: 64% of plans were showing more bladder dose and 50% of plans presented more rectum dose in M1 compared to M2. Many of the plans reviled maximum bladder dose point, other than ICRU-38 bladder point in both methods.Variation was exceeded in 5% of considerable number of plans.Conclusions: We observed a difference in critical organ dose between two studied methods. There is an advantage of using variable angle reconstruction method in identifying the catheters. It is useful to follow ABS recommendation to find maximum bladder dose

Chronic diseases now a leading cause of death in rural India--mortality data from the Andhra Pradesh Rural Health Initiative

Introduction: India is undergoing rapid epidemiological transition as a consequence of economic and social change. The pattern of mortality is a key indicator of the consequent health effects but up-to-date, precise, and reliable statistics are few, particularly in rural areas. Methods: Deaths occurring in 45 villages (population 180 162) were documented during a 12-month period in 2003-04 by multipurpose primary healthcare workers trained in the use of a verbal autopsy tool. Algorithms were used to define causes of death according to a limited list derived from the international classification of disease version 10. Causes were assigned by two independent physicians with disagreements resolved by a third. Results: A total of 1354 deaths were recorded with verbal autopsies completed for 98%. A specific underlying cause of death was assigned for 82% of all verbal autopsies done. The crude death rate was 7.5/1000 (95% confidence interval, 7.1-7.9). Diseases of the circulatory system were the leading causes of mortality (32%), with similar proportions of deaths attributable to ischaemic heart disease and stroke. Second was injury and external causes of mortality (13%) with one-third of these deaths attributable to deliberate self harm. Third were infectious and parasitic diseases (12%). Tuberculosis and intestinal conditions each caused one-third of deaths within this category. HIV was assigned as the cause for 2% of all deaths. The fourth and fifth leading causes of death were neoplasms (7%) and diseases of the respiratory system (5%). Conclusion: Non-communicable and chronic diseases are the leading causes of death in this part of rural India. The observed pattern of death is unlikely to be unique to these villages and provides new insight into the rapid progression of epidemiological transition in rural India