In Silico Screening of Phytochemicals Targeting SmdCD of Streptococcus mutans using Molecular Docking Approach

Abstract

Introduction: Dental caries is a chronic infectious disease caused by bacteria forming a biofilm formation on the tooth surface. Drug-resistant bacteria Streptococcus mutans (S. mutans) pose a vital public health issue. To overcome this, the development of effective drugs with a novel mechanism of action is very important. Drug repurposing is considered a viable alternative approach to overcome the above issue. In the present study, we have attempted to select unique and traditional source used as in traditional medicine. To continue this effort, in this study we used phytochemical of selected to find an effective cure for dental caries. Materials and methods: Inhibition of S. mutans deoxycytidylate deaminases (SmdCDs) is a promising drug development strategy against S. mutans, responsible for biofilm formation. Since no effective drugs are available against S. mutans, we conducted a virtual screening of phytochemicals to find novel compounds against this bacterium. Hence, we created a library of 871 phytochemicals from 13 plants with reported antimicrobial activity. The phytochemical library was subjected to virtual screening against the SmdCD target. Results and discussion: Traditionally, many cultures use chewing sticks for oral hygiene maintenance. In the present work, out of 871 phytochemicals, 211 phytochemicals showed the most druggable substance with zero violation from any of the drug-likeness rules. Further, the binding energy indicates the affinity of adhesion of protein structure docked with 2 hit potential herbal compounds of which Cyclocurcumin and Androsta-1,4,6-triene-3,17-dione showed the best docking with SmdCD. Conclusions: Based on the binding energy score, we suggest that hit compounds can be used for dental caries and further could be developed as an organic mouthwash. HIGHLIGHTS Streptococcus mutans is common in the human oral cavity and contributes significantly to tooth decay mutans deoxycytidylate deaminases (SmdCDs) are responsible for biofilm formation causing drug resistance SmdCDs can be used to develop effective drug against mutans, responsible for biofilm formation Screening phytochemicals may result potential compounds which can be used to develop new drugs against mutans GRAPHICAL ABSTRACT

Cyclocurcumin as Promising Bioactive Natural Compound: An Overview

“…Generally, ethanol and concentrated acetic acid are employed as solvents by considering the high hydrophobic nature of the compound [31]. The cLogP value of 3.34 and the LogS of −3.47 were calculated by in silico studies in which the drug-likeness prediction was tested to evaluate the absence of tumorigenicity, mutagenicity, irritation and reproductive toxicity risk in the use of CyCur as a potential drug candidate [32]. The lipophilic character of the compound is also confirmed by its tendency to self-assemble in aqueous solution to form spherical and monodispersed aggregates having nanometric size.…”

“…The essential role of these enzymes in repairing DNA from alteration damages is well known, and the docked data indicated the binding of CyCur at the DNA cleavage site by forming complexes with topoisomerases I and II, which are converted into permanent DNA strand breaks by cellular processes inducing apoptosis. Furthermore, computational data on the inhibition of Streptococcus mutans deoxycytidylate deaminases highlighted the potentiality of the CyCur molecule in the formulation of organic mouthwash acting as the anti-biofilm drug for the prevention of the dental caries [32].…”

“…Molecular modeling calculations in association with electron paramagnetic resonance and circular dichroism studies were performed by Randino et al to determine the specific role of the curcuminoids as neuroprotective agents in preventing the formation of the β-amyloid fibrillar aggregates commonly observed in the neurodegenerative diseases [29,[50][51][52][53]. The individual interaction of cyclocurcumin with the β-amyloid fragment Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) was investigated in hexafluoro-2-propanol/water mixtures and liposomal solutions [54]. Small unilamellar vesicles composed of pure zwitterionic 1,2-dioleoyl-snglycero-3-phosphocholine (DOPC), pure anionic 1,2-dioleoyl-sn-glycero-3-phospho-rac-1-glycerol (DOPG) and DOPC/DOPG in a 90/10 molar ratio mixture were prepared by hydration of the phospholipidic film with phosphate buffer at pH 7.4, followed by sonication.…”

“…Small unilamellar vesicles composed of pure zwitterionic 1,2-dioleoyl-snglycero-3-phosphocholine (DOPC), pure anionic 1,2-dioleoyl-sn-glycero-3-phospho-rac-1-glycerol (DOPG) and DOPC/DOPG in a 90/10 molar ratio mixture were prepared by hydration of the phospholipidic film with phosphate buffer at pH 7.4, followed by sonication. Liposomes and vesicles are commonly used as model membranes, drug delivery systems and membrane mimicking environments for specific reactions; in this case, the DOPC, DOPG and DOPC/DOPG liposomal solutions allowed to thoroughly investigate the role of the tested curcuminoids on Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and the effects on membrane perturbation [55][56][57][58]. Unlike the other curcuminoids positioned in the proximity of the membrane, the cyclocurcumin molecule penetrates the phospholipid bilayer and directly interacts with Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35).…”

“…Liposomes and vesicles are commonly used as model membranes, drug delivery systems and membrane mimicking environments for specific reactions; in this case, the DOPC, DOPG and DOPC/DOPG liposomal solutions allowed to thoroughly investigate the role of the tested curcuminoids on Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and the effects on membrane perturbation [55][56][57][58]. Unlike the other curcuminoids positioned in the proximity of the membrane, the cyclocurcumin molecule penetrates the phospholipid bilayer and directly interacts with Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Interestingly, the data obtained in the hexafluoro-2-propanol/water solution and in DOPG liposomes indicate that CyCur promotes a remarkable alteration of the Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) conformational equilibrium by reproducing the pattern of the α-helical coiled-coil structures involved in the binding of the peptides with the biological membrane [59].…”