An efficient asymmetric synthesis of (S)-atenolol: using hydrolytic kinetic resolution

Enantiomerically pure (S)-atenolol was prepared by using (R,R) salen Co(III) complex for the resolution of terminal epoxide. This process was carried out at room temperature in excellent enantio selectivity. The method can be applied for large-scale preparation of (S)-atenolol without any problem.     

Visual Impairment in the South Indian State of Andhra Pradesh: Andhra Pradesh - Rapid Assessment of Visual Impairment (AP-RAVI) Project

Purpose

To assess the prevalence and causes of visual impairment in urban and rural population aged ≥40 years in the South India state of Andhra Pradesh.

Methods

A population based cross-sectional study was conducted in which 7800 subjects were sampled from two rural and an urban locations. Visual Acuity (VA) was assessed using a tumbling E chart and eye examinations were performed by trained vision technicians. A questionnaire was used to collect personal and demographic information and previous consultation to eye care providers. Blindness and moderate Visual Impairment (VI) was defined as presenting VA <6/60 and <6/18 to 6/60 in the better eye respectively. VI included blindness and moderate VI.

Results

Of the 7800 subjects enumerated, 7378 (94.6%) were examined. Among those examined, 46.4% were male and 61.8% of them had no education. The mean age of those examined (51.7 years; standard deviation 10.9 years) was similar to those not examined (52.8 years; standard deviation 9.9 years) (p = 0.048). Age and gender adjusted prevalence of VI was 14.3% (95% CI: 13.5–15.0). Refractive errors were the leading cause of VI accounting for 47.6% of all VI followed by cataract (43.7%). Together, they contributed to over 91.3% of the total VI. With multiple logistic regression, the odds of having VI increased significantly with increasing age. Those respondents who had no education were twice (95% CI: 1.7–2.5) more likely to have VI compared to those who were educated. VI was associated with rural residence (OR: 1.3; 95% CI: 1.1–1.6). The association between VI and gender was not statistically significant.

Conclusions

The visual impairment remains a public health challenge in Andhra Pradesh, most of which can be addressed with relatively straight forward interventions like cataract surgery and spectacles. The eye care services need to be streamlined to address this challenge.     

Design,Synthesis of Biaryl Piperidine Derivatives and Their Evaluation as Potential Antileishmanial Agents against Leishmania donovani Strain Ag83

We have developed a new series of simple biaryl piperidine derivatives ( 11 – 19 ) based on biaryl naphthylisoquinoline alkaloid Ealamine-A. The target compounds were synthesized, analyzed by spectral data, and evaluated for antileishmanial activity against Leishmania donovani strain Ag83 by MTT assay. The compounds have shown the best to moderate antileishmanial activity. The 5′-fluoro-2′-methoxyphenyl derivative 14 and 3′,5′-difluorophenyl derivative 16 have inhibited the promastigotes by 86 % and 85 % after 24 h and 92 % and 91 % after 48 h incubation, respectively, at 400 μM concentration. The % inhibition was lower with the lowering of the concentration and increased with the incubation time. Compounds 12 , 15 , and 18 have solubility issues and proved to be less active than the rest of the compounds. Molecular docking studies were performed on selective active compounds and the results indicate that these compounds may act by binding to the Leishmanolysin and the docking scores are in good correlation with the antileishmanial activity. These results provide an initial insight into the design of new therapeutics for neglected tropical diseases.     

Visual Impairment among Weaving Communities in Prakasam District in South India

Purpose

To assess the prevalence and causes of visual impairment in weaving communities in Prakasam district in South India state of Andhra Pradesh.

Methods

Using Rapid Assessment of Visual Impairment (RAVI) methodology, a population based cross-sectional study was conducted. A two-stage sampling strategy was used to select 3000 participants aged ≥40 years. Visual Acuity (VA) was assessed using a tumbling E chart and ocular examinations were performed by trained Para medical ophthalmic personnel. A questionnaire was used to collect personal and demographic information. Blindness and moderate Visual Impairment (VI) was defined as presenting VA <6/60 and <6/18 to 6/60 respectively. VI included blindness and moderate VI.

Results

2848 of 3000 enumerated subjects (94.0%) participated. 39% were in 40–49 years age group and 11.8% were aged ≥70 years, 55% were women and nearly half of them had no formal education. 400 (14%; 95% CI: 12.8–15.3) subjects had VI, including blindness in 131 (4.6%; 95% CI: 3.8–5.4) and moderate VI in 269 (9.4%; 95% CI: 8.3–10.5) individuals. On applying multiple logistic regression, VI was significantly associated with older age and no formal education. Though the odds of having VI were higher in females, it was of borderline statistical significance (p = 0.06). Refractive error was the leading cause of all VI followed by cataract (56%). However, refractive errors were the leading cause of moderate VI (73.2%) and cataract was the leading cause of blindness (62.6%). ‘Cannot afford the cost of services’ was the leading barrier for utilization of eye care services (47%).

Conclusions

There is a significant burden of VI in weaving communities in Andhra Pradesh, India most of which is avoidable. With this information as baseline, services need to be streamlined to address this burden.     

Synthesis of novel 2-alkyl triazole-3-alkyl substituted quinoline derivatives and their cytotoxic activity

The propargyl alcohol on reaction with alkylazides under Sharpless conditions through click chemistry concept gave exclusively 1,4-disubstituted triazoles 2. The compounds 2 were oxidized to aldehydes 3 followed by reaction with aniline resulted Schiff’s bases 4. The compounds 4 was further reacted with various aldehydes having α-hydrogen using molecular iodine as a catalyst and obtained 2-alkyl triazole-3-alkyl substituted quinoline derivatives 5. All the final compounds were screened against four human cancer cell lines (THP-1, Colo205, U937 & HeLa) and promising compounds have been identified.     

Studies on synthesis of novel pyrido[2,3-d]pyrimidine derivatives,evaluation of their antimicrobial activity and molecular docking

A series of novel pyrido[2,3-d]pyrimidine derivatives 6 were prepared starting from 2-amino-3-cyano-4-trifluoromethyl-6-phenyl pyridine 3 via Grignard’s reaction, cyclization followed by coupling with aliphatic and cyclic amines. All the compounds 6 were screened for antibacterial, minimum bactericidal concentration (MBC), biofilm inhibition activity as well as antifungal and minimum fungicidal concentration (MFC) activities. Among the screened compounds, the compounds 6e, 6f, and 6m which showed exhibiting promising activity have been identified. The results reveal that the compound pyrido[2,3-d]pyrimidine derivative 6e altered the sterol profile which may exert its antifungal activity through inhibition of ergosterol biosynthesis and could be an ideal candidate for antifungal therapy. The molecular docking results also validated the antifungal results.     

Synthesis of novel hetero ring fused pyridine derivatives; Their anticancer activity,CoMFA and CoMSIA studies

A series of novel furo[2,3-b]pyridine-2-carboxamide 4a–h/pyrido[3′,2′:4,5]furo[3,2-d] pyrimidin-4(3H)-one derivatives 5a–p were prepared from pyridin 2(1H) one 1 via selective O-alkylation with α-bromoethylester followed by cyclization, then reaction with different aliphatic primary amines to obtain 4 and further reaction with triethyl orthoacetate/triethyl orthoformate. Also prepared novel furo[2,3-b]pyridine-2-carbohydrazide Schiff’s bases 7a–h and pyrido [3′,2′:4,5]furo[3,2-d]pyrimidin-4(3H)-one derivatives 8a–h starting from furo[2,3-b]pyridine carboxylate derivatives 3 by reaction with hydrazine hydrate to form 6 and reaction with diverse substituted aldehydes and cyclization. Products 4a–h, 5a–p, 7a–h and 8a–h were screened against four human cancer cell lines (HeLa, COLO205, Hep G2 and MCF 7) and one normal cell line (HEK 293). Compounds 4e, 4f, 4g, 5h, 7c, 7d, 7e and 7f showed significant anticancer activity against all the cell lines at micro molar concentration and found to be non-toxic to normal cell line. Studies for HeLa, COLO205 and MCF-7 using CoMFA and CoMSIA. Models from 3D-QSAR provided a strong basis for future rational design of more active and selective HeLa, COLO205 and MCF-7 cell line inhibitors.     

Synthesis and structure-activity relationships of novel pyrimido[1,2-b]indazoles as potential anticancer agents against A-549 cell lines

A series of novel pyrimido[1,2-b]indazoles 5, 7 have been prepared from 3-trifluoromethyl-5-phenyl-2,6-dicyano anilines 1 via novel indazole regioisomers 3 and 4 through a facile strategy. Specific examples were evaluated for anticancer activity in vitro and found to exhibit promising activity against A-549 cell lines and are more effective than Etoposide. QSAR models were developed and validated by cross-validation method. The results of the best QSAR model were further compared with the crystal structure of tubulin protein. The binding energies estimated were found to have a good correlation with the experimental inhibitory potencies.