Effect of Lead Exposure and Lifestyle Factors on Methylation Index Markers Among Pb-Exposed Workers.

S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) and the ratio of SAM and SAH in Pb-exposed workers need to be assessed. In this study, we investigated the effects of Pb exposure on SAM, SAH, and methylation index (MI) in Pb-exposed workers with contemplation of lifestyle factors. Blood lead levels (BLLs), SAM, SAH, MI, and lifestyle factors were assessed in 338 male Pb-exposed workers. BLLs are estimated by ICP-OES method. SAM and SAH levels in serum were determined by ELISA method. The MI was calculated using SAM and SAH individual values. The lifestyle factors were collected using standard questionnaire. Levels of SAM and MI were significantly decreased with increased age, experience > 5 years, habits of tobacco chewing, smoking, alcohol consumption, and BLLs 10-30, 30-50, and > 50 µg/dL. Levels of SAH were significantly increased with increased age, habits of tobacco chewing and smoking, and BLLs 10-30, 30-50, and > 50 µg/dL. The association between BLLs and methylation index markers (SAM and MI) was reported as negative and significant. The association between BLLs and SAH was noted positive and significant. The influence of BLLs and lifestyle factors on SAM was noted at 12%, SAH at 35%, and MI at 27%, respectively. The highest percentage of influence was noted in SAH, followed by MI and SAM. In the workers exposed to Pb, lifestyle factors resulted in decreased SAM and MI and increased SAH levels. Adaptation of healthy lifestyle factors, personal hygiene practices, and use of PPE were suggested to minimize the reduction of methylation index markers.

Effect of Pb-exposure and B vitamin deficiencies on δ-aminolevulinic acid dehydratase activity among workers from Pb recycling plants.

Previous studies reported that Pb exposure causes a negative association with delta-aminolevulinic acid dehydratase activity (δ-ALAD), but the impact of Pb exposure (dose and time), B vitamin deficiencies, and lifestyle factors needs to be explored. In this study, the impact of Pb exposure, B vitamin deficiencies, and lifestyle factors on δ-ALAD activity among workers exposed to Pb from the Pb-recycling process was evaluated. Blood lead levels (BLLs), B vitamins (B6, B9, and B12), hematological factors (Hb% and HCT), lifestyle factors, and δ-ALAD activity was assessed in 170 male Pb-exposed workers engaged in the Pb recycling process. BLLs are estimated using the ICP-OES method. B vitamins in serum samples from workers were determined using the ELISA method. The δ-ALAD activity in whole blood samples was determined using the spectrophotometer method. The lifestyle factors were collected using a standard questionnaire. The δ-ALAD activity was significantly decreased in workers with the habits of alcohol use, tobacco consumption, hematocrit < 41%, mild and moderate categories of anemia, vitamin B6 and B12 deficiency, and BLL categories of 10-30, 30-50, and > 50 µg/dL. Multiple regression analysis revealed that the independent variables of alcohol consumption (ß = - 0.170; P = 0.025), BLLs (ß = - 0.589; P = 0.001) and Hb% (ß = 0.183; P = 0.001) significantly influenced the δ-ALAD activity with 44.2% (R2 = 0.442). Among the workers exposed to Pb from the Pb recycling plant, δ-ALAD activity was considerably reduced by Pb exposure, B vitamin deficiency, hematological parameters, and lifestyle factors.

Molecular docking studies of gyrase inhibitors: weighing earlier screening bedrock.

For any antimicrobial assay, a standard drug is used to compare the bactericidal efficiency of the bioactive compound under screening. The standard drugs have different targets that may be intracellular or membrane located. The location of the target is believed to be determining the bioactivity of the drug depending on the drug's access to its target. Therefore, different drugs must have a different magnitude in exhibiting the biological effect. However, in most of the published literature about the screening of bioactive compounds on antimicrobial activity, generally, the standard drug is randomly chosen while comparing against the bioactive compound of interest. Further, the antimicrobial activity is inferred by comparing the randomly chosen standard drugs without knowing the physicochemical parameters of the standard drug and the test molecule. It is just like an unfair comparison of the impact of a bullet with the impact of an explosive in a combat scene. Computer-based strategies for structure-based drug discovery presents a valuable alternative to the costly and time-consuming process of random screening. The docking studies provide better insights into the binding mechanism of substrate and inhibitor at the molecular level. The evaluation of such a comparison of bioactive compounds against randomly selected standard drugs through a customized virtual screening pipeline showed 57% false positives, 18% true positive, 17% true negative, 8% false-negative results. This study directs for mandatory cheminformatics-based assessment of the bioactive compounds before choosing the standard drug to compare with. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-020-00064-9.

Synthesis and biological evaluation of new imidazo[2,1-b][1,3,4]thiadiazole-benzimidazole derivatives.

In this report, we describe the synthesis and biological evaluation of a new series of 2-(imidazo[2,1-b][1,3,4]thiadiazol-5-yl)-1H-benzimidazole derivatives (5a-ac). The molecules were analyzed by (1)H NMR, (13)C NMR, mass spectral and elemental data. The structure of one of the pre-final compounds, 6-(4-methoxyphenyl)-2-(4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde (4d) and that of a target compound, 2-[2-methyl-6-(4-methyl phenyl) imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-1H-benzimidazole (5aa) were confirmed by single crystal XRD studies. All the target compounds were screened for in vitro anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv strain. Seven (5c, 5d, 5l, 5p, 5r, 5z and 5aa) out of twenty nine compounds showed potent anti-tubercular activity with a MIC of 3.125 µg/mL. A p-substituted phenyl group (p-tolyl or p-chlorophenyl) in the imidazo[2,1-b][1,3,4]thiadiazole ring and/or a chloro group in the benzimidazole ring enhance anti-tuberculosis activity whereas a nitro group in the benzimidazole ring reduces the activity. In the antibacterial screening, compounds 5i, 5w and 5ac showed promising activity against the tested bacterial strains. Further, antifungal and antioxidant activities of these molecules were also investigated. In the cytotoxicity study, the active antitubercular compounds exhibited very low toxicity against a normal cell line.