Anti-tubercular Potency and Computationallyassessed Drug-likeness and Toxicology of Diversely Substituted Indolizines

Venugopala, Katharigatta N.; Tratrat, Christophe; Chandrashekharappa, Sandeep; Attimarad, Mahesh; Sreeharsha, Nagaraja; Nair, Anroop B.; Shinu, Pottathil; Venugopala, Rashmi; Al-Attraqchi, Omar Husham Ahmed; Morsy, Mohamed A.; Haroun, Michelyne; Odhav, Bharti

doi:10.5530/ijper.53.3.87

Cited by 29 publications

(18 citation statements)

References 34 publications

(38 reference statements)

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“…[ 4 ]. The presence of VEN in many effluent-impacted downstream waters has been documented previously [ 5 , 6 , 7 ], and its concentration was found to be much higher than the other drugs [ 4 , 8 , 9 , 10 ]. VEN increased mortality in exposed embryos and also affected the reproduction, along with significant histological changes in the kidney of female zebrafish [ 11 ].…”

Section: Introductionmentioning

confidence: 71%

Rapid, Precise and Affordable Estimation of Venlafaxine and Its Metabolites in Highly Polluted Effluent Waters: Proof-of-Concept for Methodology

Hussain

Ramnarayanan²,

Roopashree³

et al. 2020

Molecules

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Widespread presence of pharmaceuticals and their metabolites in the environment of industrialized countries is an emerging global concern. Potential contamination of the soil and water by such pharmacologically active substances poses serious ecotoxicological implications. Several studies assessing the long-term ecological risks of pharmaceutical contaminants mainly focus on the risk assessment of the parent drug, while the potential contributions of their metabolites is often neglected. Presence of selective serotonin and norepinephrine reuptake inhibitor venlafaxine, an antidepressant drug, and its metabolites is a matter of serious concern for aquatic systems, since they are difficult to remove by traditional wastewater treatment processes. The concentration of VEN present in water is reportedly one of the highest among pharmaceuticals; however, the long-term effects of its metabolites have not yet been systematically studied. Given the consideration to complex and time-consuming effluent treatment, and realizing the importance of levels of venlafaxine and its metabolites, a simple and accurate analytical method for quick determination is needed. We designed a selective colorimetric method by using oxidative coupling of drug molecules with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) reagent, to quantify the presence of venlafaxine and its metabolites in aquatic samples, with special emphasis on effluent. The method was validated for selectivity, specificity and robustness as per the ICH Q2 guidelines to assess its suitability in pharmaceutical samples, as well. Highly sensitive and green economical analytical method was successfully established for estimation of venlafaxine and its metabolites in aquatic samples. The method was quick, as it involved minimum processing steps. The method was accurate and linear in the range of 0.5 to 80 ppm and could successfully detect lowest concentration of 1.3 ppm, thus qualifying its applicability for the desired purpose to check the presence of trace levels of VEN or its metabolites in aquatic samples or in pharmaceutical formulations.

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Section: Introductionmentioning

confidence: 71%

Rapid, Precise and Affordable Estimation of Venlafaxine and Its Metabolites in Highly Polluted Effluent Waters: Proof-of-Concept for Methodology

Hussain

Ramnarayanan²,

Roopashree³

et al. 2020

Molecules

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“…Genes encoding AMEs are prevalent in various groups of bacteria [ 10 , 29 , 30 , 31 , 32 ]. In this study, prevalence of AME genes were found to be 60.82% among ESBL producing strains of Enterobacterales .…”

Section: Discussionmentioning

confidence: 99%

Monitoring of Non-β-Lactam Antibiotic Resistance-Associated Genes in ESBL Producing Enterobacterales Isolates

et al. 2020

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Genetic context of extended spectrum β-Lactamase (ESBL) producing Enterobacterales and its association with plasmid mediated quinolone resistance (PMQR), aminoglycoside modifying enzymes (AME) and Trimethoprim/Sulfamethoxazole (TMP-SMX) resistance is little known from North India. Therefore, the current study was aimed to investigate the frequency of Non-β-Lactam antibiotic resistance associated genes in extended spectrum β-Lactamase producing Enterobacterales. For this study, Non-Duplicate phenotypically confirmed ESBL producing Enterobacterales isolates (N = 186) were analyzed for ESBLs, PMQRs, AMEs and TMP-SMX resistance genes using polymerase chain reaction (PCR). PCR detected presence of PMQR genes in 81.29% (N = 139) of ESBL isolates (N = 171), AME genes in 60.82% and TMP-SMX resistance genes in 63.74% of the isolates. Molecular characterization of ESBL producing Enterobacterales showed 84.79% blaTEM followed by 73.68% blaCTX-M, 43.86% blaSHV, 19.88% blaPER and 9.94% blaVEB, respectively. Analysis of PMQR genes revealed 77.7% aac(6′)-lb-cr the most commonly detected gene followed by 67.63% oqxB, 62.59% oqxA, 43.17% qnrB, 19.42% qnrD, 18.7% qnrS, 9.35% qnrA, 3.6% qepA and 2.88% qnrC, respectively. Analysis of AMEs gene profile demonstrated 81.73% aac(6′)-Ib, the most frequently encountered gene followed by 46.15% aph(3′)-Ia, 44.23% ant(3”)-Ia, respectively. A 100% prevalence of sul1, followed by dfrA (54.63%) and sul2 (15.74%) was observed. In summary, prevalence of ESBL-Producing genes (particularly blaTEM and blaCTX-M) along with PMQR, AMEs, and TMP-SMX resistant genes may potentially aid in the transfer of antimicrobial resistance among these strains.

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“…ADMET properties of the derivatives (3a-n) were predicted using the software Accelry's Discovery Studio 4.0 Client [68]. ADMET-related descriptors such as drug-likeness, permeability, intestine absorption, plasma binding, liver toxicity, and CYP450 inhibition were investigated.…”

Section: In Silico Admet Predictionmentioning

confidence: 99%

Larvicidal Activities of 2-Aryl-2,3-Dihydroquinazolin -4-ones against Malaria Vector Anopheles arabiensis, In Silico ADMET Prediction and Molecular Target Investigation

et al. 2020

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Malaria, affecting all continents, remains one of the life-threatening diseases introduced by parasites that are transmitted to humans through the bites of infected Anopheles mosquitoes. Although insecticides are currently used to reduce malaria transmission, their safety concern for living systems, as well as the environment, is a growing problem. Therefore, the discovery of novel, less toxic, and environmentally safe molecules to effectively combat the control of these vectors is in high demand. In order to identify new potential larvicidal agents, a series of 2-aryl-1,2-dihydroquinazolin-4-one derivatives were synthesized and evaluated for their larvicidal activity against Anopheles arabiensis. The in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the compounds were also investigated and most of the derivatives possessed a favorable ADMET profile. Computational modeling studies of the title compounds demonstrated a favorable binding interaction against the acetylcholinesterase enzyme molecular target. Thus, 2-aryl-1,2-dihydroquinazolin-4-ones were identified as a novel class of Anopheles arabiensis insecticides which can be used as lead molecules for the further development of more potent and safer larvicidal agents for treating malaria.

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Anti-tubercular Potency and Computationallyassessed Drug-likeness and Toxicology of Diversely Substituted Indolizines

Cited by 29 publications

References 34 publications

Rapid, Precise and Affordable Estimation of Venlafaxine and Its Metabolites in Highly Polluted Effluent Waters: Proof-of-Concept for Methodology

Rapid, Precise and Affordable Estimation of Venlafaxine and Its Metabolites in Highly Polluted Effluent Waters: Proof-of-Concept for Methodology

Monitoring of Non-β-Lactam Antibiotic Resistance-Associated Genes in ESBL Producing Enterobacterales Isolates

Larvicidal Activities of 2-Aryl-2,3-Dihydroquinazolin -4-ones against Malaria Vector Anopheles arabiensis, In Silico ADMET Prediction and Molecular Target Investigation

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