New QSAR and Solvatochromic Estimation of Molecular Parameters of Chlortetracycline

The present paper is focused on determination of the main parameters of Chlortetracycline. Chlortetracycline belongs to one of the most used family of antibiotics worldwide, Tetracyclines. Because of the large spectrum of infections which can be treated with this category of antibiotics there are attempts to find new derivatives from this class. The compounds derived from the same basic structure exhibit same chemical properties, that is why knowing in detail the main physico-chemical properties of Chlortetracycline could be a real help in synthesize new efficient derivatives. In order to evaluate the reactivity and biological activity HyperChem was used to establish the optimized structure, the electro-optical, the energetic and QSAR parameters. The solvatochromic methods allowed determining the intermolecular interactions types and their contribution to the spectral shifts of measured electronic absorption bands. Based on computational and solvatochromic results, the excited state dipole moment of Chlortetracycline was established by variation method.

Ames mutagenicity, structural alerts of carcinogenicity, Hansch QSAR parameters (ClogP, CMR, MgVol), tumor site concordance/multiplicity, and tumorigenicity rank in NTP 2-year rodent studies

Since its inception in 1976, the National Toxicology Program (NTP) has conducted 594 2-year studies on rats and mice by a number of routes of administration including inhalation, feed, drinking water, dermal, and intraperitoneal injection. Of these studies, the results on 470 chemicals were of adequate technical quality to be incorporated into final technical reports. In this study, the 470 chemicals were categorized from 1 to 48 by the level of “clear” neoplastic evidence in male and female rats, and in male and female mice, and given an ordinal rank from 1 to 135 following additional considerations regarding tumor site concordance and tumor multiplicity. The resultant tumorigenicity category score and ordinal rank score were examined for associations with results in the Ames Salmonella mutagenicity assay; presence or absence of structural alerts of carcinogenicity; and three Hansch Quantitative Structure-Activity Relationship (QSAR) parameters, namely, calculated base 10 logarithm of the octanol–water partition coefficient (ClogP), calculated molar refractivity (CMR), and McGowan molecular volume (MgVol). Smaller molecular volumes were found to be associated with higher levels of tumorigenicity. Whereas lower rather than higher levels of lipophilicity were found to be associated with higher levels of tumorigenicity. Positive Ames test results were positively correlated with overall tumorigenicity and with possession of structural alerts. Since larger organic molecules have more chemical reaction centers, it was not surprising that higher ClogP values were positively correlated with the number of structural alerts. The results from this study demonstrate the ability to devise rational rules for relative tumorigenicity that correlate, in biologically plausible ways, with known parameters of toxicity.

ANTIMICROBIAL AND IN SILICO ADMET SCREENING OF NOVEL (E)-N-(2-(1H-INDOL-3-YL-AMINO) VINYL)-3-(1-METHYL-1H-INDOL-3-YL)-3-PHENYLPROPANAMIDE DERIVATIVES

<p><strong>Objective: </strong>Synthesis, <em>in silico</em> absorption, distribution, metabolism, excretion, toxicity (ADMET) and <em>in vitro</em> antimicrobial screening of (<em>E</em>)-<em>N</em>-(2-(1<em>H</em>-indol-3-ylamino) vinyl)-3-(1-methyl-1<em>H</em>-indol-3-yl)-3-phenylpropanamide derivatives.<strong></strong></p><p><strong>Methods: </strong>(<em>E</em>)-<em>N</em>-(2-(1<em>H</em>-indol-3-ylamino) vinyl)-3-(1-methyl-1<em>H</em>-indol-3-yl)-3 phenylpropane-amide derivatives were synthesized by combining indole ethanolamine and substituted Meldrum’s adduct. The synthesized compounds were subjected to <em>in vitro</em> antimicrobial study by cup plate method and <em>in silico</em> ADMET properties using ACD/I-Lab 2.0.</p><p><strong>Results: </strong>The <em>in vitro </em>antimicrobial screening against precarious pathogenic microorganisms <em>viz</em>, <em>Pseudomonas aureginosa</em>, <em>Staphylococcus aureus,</em> <em>Escherichia coli, </em><em>Vibrio cholerae</em>, and the antifungal activity against <em>Candida albicans, </em><em>Aspergillus niger</em>, <em>Penicillin chrysogenum</em> and <em>Cladosporium oxysporum</em> strains. The results revealed that compounds 5b, 5c, 5d and 5e showed good antimicrobial property and obeyed the <em>in silico</em> pharmacokinetic parameters.</p><p><strong>Conclusion: </strong>The encouraging results exhibited by the compounds (<em>E</em>)-<em>N</em>-(2-(1<em>H</em>-indol-3-ylamino) vinyl)-3-(1-methyl-1<em>H</em>-indol-3-yl)-3-phenyl propanamide derivatives, 5(a-e) can be explored as possible hits in antimicrobial therapy. The molecules obey the Lipinski rule of five when tested <em>in silico </em>and can be used in understanding the quantitative structure-activity relationship (QSAR) parameters.</p>