Potential Fluorinated Anti-MRSA Thiazolidinone Derivatives with Antibacterial, Antitubercular Activity and Molecular Docking Studies.

MRSA infection is one of the alarming diseases in the current scenario. Identifying newer molecules to treat MRSA infection is of urgent need. In the present study, we have designed fluorinated thiazolidinone derivatives with various aryl/heteroaryl units at 5th position of the thiazolidinone core as promising anti-MRSA agents. All the compounds were screened for antibacterial activity against four bacterial strains. Among the tested compounds, the halogenated compounds with simple arylidene ring, (5Z)-5-[(3-chloro-2-fluorophenyl)methylidene]-2-[(1,3-thiazol-2-yl)amino]-1,3-thiazol-4(5H)-one (4b), (5Z)-5-[(4-chloro-2-fluorophenyl)methylidene]-2-[(1,3-thiazol-2-yl)amino]-1,3-thiazol-4(5H)-one (4c), (5Z)-5-[(3-fluoro-4-methylphenyl)methylidene]-2-[(1,3-thiazol-2-yl)amino]-1,3-thiazol-4(5H)-one (4f) and (5Z)-5-[(3,5-difluorophenyl)methylidene]-2-[(1,3-thiazol-2-yl)amino]-1,3-thiazol-4(5H)-one (4g) showed excellent activity with MIC 3.125-6.25 µg/mL against S. aureus and P. aeruginosa organism. Furthermore, these potent compounds were screened against MRSA strains, ESKAPE panel organism, and H37Rv mycobacterium strain. Compounds 4c (MIC 0.39 µg/mL), and 4f (MIC 0.39 and 0.79 µg/mL) displayed promising activity against MRSA strains (ATCC and clinical isolates, respectively). The most potent compounds, 4c and 4f eradicated the growth of bacterial colonies in a time-kill assay indicated that these are bactericidal in nature. The preliminary toxicity study of the potent molecules revealed that these compounds are non-hemolytic in nature as they did not induce lysis in human RBCs. In addition, the molecular docking and dynamics studies of compounds 4b, 4c, 4f and 4g were carried out on MurB protein of S. aureus (PDB code: 1HSK). Docking results demonstrated remarkable hydrogen bonding interaction with key amino acids ARG310, ASN83, GLY79 and π-π interactions with TYR149 which confirm the mode of action of the molecules.

A preliminary study on quinazolinylaminobenzoyl monopeptide esters as effective Gram-positive bacteriostatic agents.

AIM: To investigate a novel series of quinazoline monopeptide esters for the in vitro antibacterial activity. METHODOLOGY/RESULTS: The compounds were synthesized via one-pot Dimroth rearrangement of suitable formamidine intermediates with 3-aminobenzoic acid, followed by coupling the resulting acids with amino acid esters and screening for their antibacterial activity by broth dilution method. The compounds 5a, 5b, 5c, 5g, 5i and 5j showed promising activity against the Gram-positive bacteria, 5c and 5g being the most potent against Enterococcus faecalis and Staphylococcus aureus, respectively, with a minimal inhibitory concentration of 0.51 µM. The percentage hemolysis of the compounds ranged from 2.79 to 12.92 at a concentration of 100 µg/ml. The molecular docking studies revealed their GlmU inhibitory action. CONCLUSION: The compounds 5a and 5g emerged as antibacterial hits.

Awareness and Knowledge of Glaucoma in Central India: A Hospital-Based Study.

PURPOSE: To assess the awareness and knowledge of glaucoma among people attending the ophthalmology outpatient department at a tertiary care hospital in central India. DESIGN: A prospective observational study. METHODS: A questionnaire-based study was conducted, involving persons aged 18 and above attending the ophthalmology outpatient department from October 2014 to September 2015. Data on awareness and knowledge of glaucoma was collected through a face-to-face interview. RESULTS: Fourteen hundred people participated in the study. The mean age of participants was 43 ± 15 years (range, 18-85). The study participants included 53% men and 47% women. Only 27% (n = 380/1400) of the participants were aware of glaucoma. Age, sex, and presence or type of refractive error had no impact on glaucoma awareness. Awareness level was greater in individuals with higher education levels and those belonging to an upper socioeconomic class (SEC). Multiple logistic regression analysis revealed significantly higher levels of glaucoma awareness among participants belonging to the upper 2 SECs (P = 0.05) and those educated above the high school level (P = 0.001). The most common source of awareness was close acquaintance with relatives, famly members, and friends of glaucoma patients. CONCLUSIONS: Awareness of glaucoma in India is low. Lack of education and lower socioeconomic status are the major risk factors for late preentation of glaucoma. Continuous presence of a low level of awareness and the same factors accounting for it warrants the need for an aggressive and refined approach to increase awareness of glaucoma to prevent glaucoma-related blindness.

Comparison of the Efficacy of Carboxymethylcellulose 0.5%, Hydroxypropyl-guar Containing Polyethylene Glycol 400/Propylene Glycol, and Hydroxypropyl Methyl Cellulose 0.3% Tear Substitutes in Improving Ocular Surface Disease Index in Cases of Dry Eye.

PURPOSE: To compare the efficacy of carboxymethylcellulose 0.5% (CMC), hydroxypropyl-guar containing polyethylene glycol 400/propylene glycol (PEG/PG), and hydroxypropyl methylcellulose 0.3% (HPMC) as tear substitutes in patients with dry eye. METHODS: A retrospective evaluation of cases presenting with symptoms of dry eye from July 2014 to June 2015 was done. Patients with Ocular Surface Disease Index (OSDI) scoring >12 were included in the study. Parameters such as age, gender, Schirmer test (ST), and tear film breakup time (TBUT) were recorded on day 0, week 1, and week 4. For analysis, cases were divided into three groups; Group 1 - CMC, Group 2 - PEG/PG, and Group 3 - HPMC. RESULTS: Overall, 120 patients were included in the study. Demographic data and baseline characteristics were comparable among the groups. Group 2 had significant improvement in percentage change in OSDI (weeks 0-1, 0-4, and 1-4, P = 0.00), TBUT (weeks 0-1, P = 0.01; 0-4, P = 0.006; and 1-4, P = 0.007), and in ST (weeks 0-1, P = 0.02; 0-4, P = 0.002; and 1-4, P = 0.008) compared to Group 1 at all follow-ups. Group 3 had improvements similar to Group 2, but it was not at all follow-ups (improvement in percentage change OSDI [weeks 0-1, 0-4, and 1-4, P = 0.00], TBUT [weeks 0-1, P = 0.10; 0-4, P = 0.03; and 1-4, P = 0.04], and in ST [weeks 0-1, P = 0.007; 0-4, P = 0.03; and 1-4, P = 0.12]). No significant difference was found between Groups 2 and 3. CONCLUSIONS: Hydroxypropyl-guar containing PEG/PG and HPMC as tear substitutes are better than CMC. While HPMC was comparable to PEG/PG in subjective improvement, the objective improvement was not consistent.