In Silico Appraisal, Synthesis, Antibacterial Screening and DNA Cleavage for 1,2,5-thiadiazole Derivative

Abstract

Background: : Thiadiazole not only acts as “hydrogen binding domain” and “two-electron donor system” but also as constrained pharmacophore. Methods:: The maleate salt of 2-((2-hydroxy-3-((4-morpholino-1, 2,5-thiadiazol-3-yl) oxy) propyl) amino)- 2-methylpropan-1-ol (TML-Hydroxy)(4) has been synthesized. This methodology involves preparation of 4-morpholino-1, 2,5-thiadiazol-3-ol by hydroxylation of 4-(4-chloro-1, 2,5-thiadiazol-3-yl) morpholine followed by condensation with 2-(chloromethyl) oxirane to afford 4-(4-(oxiran-2-ylmethoxy)-1,2,5-thiadiazol- 3-yl) morpholine. Oxirane ring of this compound was opened by treating with 2-amino-2-methyl propan-1- ol to afford the target compound TML-Hydroxy. Structures of the synthesized compounds have been elucidated by NMR, MASS, FTIR spectroscopy. Results: : The DSC study clearly showed that the compound 4-maleate salt is crystalline in nature. In vitro antibacterial inhibition and little potential for DNA cleavage of the compound 4 were explored. We extended our study to explore the inhibition mechanism by conducting molecular docking, ADMET and molecular dynamics analysis by using Schrödinger. The molecular docking for compound 4 showed better interactions with target 3IVX with docking score of -8.508 kcal/mol with respect to standard ciprofloxacin (docking score= -3.879 kcal/mol). TML-Hydroxy was obtained in silico as non-carcinogenic and non-AMES toxic with good percent human oral absorption profile (69.639%). TML-Hydroxy showed the moderate inhibition against Mycobacteria tuberculosis with MIC 25.00 μg/mL as well as moderate inhibition against S. aureus, Bacillus sps, K. Pneumoniae and E. coli species. Conclusion: : In view of the importance of the 1,2,5-thiadiazole moiety involved, this study would pave the way for future development of more effective analogs for applications in medicinal field.

Identification of Anxiolytic Potential of Niranthin: In-vivo and Computational Investigations

“…Henceforth, our present study has been focused to carry out anti-anxiety activity of pure, isolated and characterized niranthin in various animal models in-vivo as assessed by light/dark box, EPMT and motor coordination test [25][26][27][28]. We have also carried out in-silico molecular modelling studies in order to support our current findings [22,24,[29][30][31][32][33][34][35][36]. Molecular docking simulations used in our current study will also shade more lights on GABA assisted/mediated role of niranthin as anti-anxiety agent.…”

“…Molecular docking studies were performed using Vlife MDS 4.6.1 version. In recent studies, varied targets were screened for biological activities, which formed the basis for present molecular screening methodology [22,24,[29][30][31][32][33][34][35][36]. 3D X-ray crystallographic structure of the GABA-(A) homopentamer receptor (PDB Code: 4COF) was retrieved from the Protein Data Bank (www.rcsb.com) [37].…”

“…We have evaluated the in-silico predictions of Molecular Properties and Drug-likeness of Niranthin for predictions of passive intestinal absorption and brain penetration, as a function of lipophilicity and apparent polarity using popular web based tool called Web Molecular Editor v1.5.1 (https :// www.molso ft.com/mprop /) [29][30][31][32][33][34][35][36].…”

Yeni 1,3,4-Tiyadiazol-Piperazin Türevlerinin Sentezi, İn Vitro Antikolinesteraz ve Antimikrobiyal Değerlendirilmesi

“…It can be bioisosterically replaced with oxazole, oxadiazole and benzene. The sulfur atom usually improves the ease of lipophilicity [5]. The core motif thiadiazole and its derivatives have been reported in the literature for wide varieties of pharmacological activities such as antitumoral, antimicrobial, antiviral, antifungal, anti-inflammatory, antiplatelet, anti-tubercular, and antidepressant activities [6].…”

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“…Extensive biochemical and pharmacological studies have confirmed that these molecules are effective against various strains of microorganisms. Based on recent literature and in continuation of our research 14,15,16,17,18,19,20,21 for more potent antibacterial agents, we synthesized and screened quinolinobenzimidazole derivatives (3a-3h). The compounds (3a-3h) were prepared using reported methodology 22 by using o-phenylene diamines and various substituted quinolone aldehydes in presence of catalytic NH 4 Cl in ethanol.…”