**3.2 Molecular docking**

Computational docking was implemented to predict binding of the 10 compounds (**Figure 3**) which represents alkaloids, antibacterial, antimicrobials from microorganisms mainly bacteria, fungi, and algae with acid β-glycosidase as the target protein.

#### *A Scientific Ethnomedical Study Using Microbes on Gaucher Disease: An* In-Silico *Analysis DOI: http://dx.doi.org/10.5772/intechopen.107545*

Glide Score is an empirical scoring function that approximates the ligand binding free energy, including force field (electrostatic, van der Waals) contributions It highlights docking accuracy, database enrichment, and binding affinity prediction. Glide approximates a complete systematic search of the conformational, orientational, and positional space of the docked ligand.

Out of 10 microbial bioactive compounds, Lipoxazolidinone C, Marinopyrrole A, LBM-415, were the promising bacterial compounds, Cinnamic acid, Chlorohydroaspyrone B, 14-hydroxyterezine D, Apralactone A, Spirotryprostatin B, and Dehydrocurvularin belongs to the fungal compounds, and Racemosin A is the only compound belonging to algae. The binding scores of each compound with the target protein acid β-glycosidase are depicted in **Table 2**.

Among the 10 ligands, the compound Lipoxazolidinone C from *Marinispora sp* (Bacteria) had the least Glide score of −10.56 Kcal/mol (**Table 2**). The binding mode for Lipoxazolidinone C to acid β-glycosidase was attributed to H-bond interaction with GLU 482 with a bond length of 2.1 Å, while amino acid residue ASN 377 was positioned at a distance of H-bond with a bond length of 2.0 Å with Cinnamic acid from *Cladosporium sp.* of fungi with a glide score of −10.33 Kcal/mol. The third


#### **Table 2.**

*Docking scores of β- glucosidase with microbial compounds.*

docking scores were received by the ligand Marinopyrrole A from *Streptomyces saccurensis* (Bacteria) with a Glide score of −9.6 Kcal/mol. Marinopyrrol A interacts with SER 447, GLU 446, ASN 377 forming four H-bonds of length 2.6, 1.9, 2.3, 2.3 Å respectively. Followed by the Glide score of −9.17 Kcal/mol was Chlorohydroaspyrone B from the microbe *Exophiala sp*. (Fungi). The residues were SER 477, ASN 262, and ASN 377 forming three H-bonds with the bond lengths of 2.2, 2.1, and 1.7 Å respectively, while amino acid residues ARG 444 were positioned at a distance of 2.0 Å of H-bond with ligand 14-hydroxyterezine D from *Aspergillus sydowi* (Fungi) with a Glide score of −8.82 Kcal/mol (**Figure 4**).

*A Scientific Ethnomedical Study Using Microbes on Gaucher Disease: An* In-Silico *Analysis DOI: http://dx.doi.org/10.5772/intechopen.107545*

#### **Figure 4.**

*The docking complex of (a) Lipoxazolidinone C, (b) Cinnamic acid, (c) Marinopyrrole a, (d) Chlorohydroaspyrone B, and (e) 14-hydroxyterezine D with the X-ray structure of acid β-glucosidase. 3D interaction (left) and 2D schematic diagram using Ligplot (right).*

In addition, Racemosin A from *Caulerpa racemose* (Algae) interacts with ASN 262 with two H-bonds, while amino acid residues ASN 377, GLY 379, and GLU 446 are positioned at a distance of H-bond with Apralactone A which is obtained from *Curuvularia sp.* (Fungi). LBM-415 from *Streptomyces sp.* (Bacteria) interacts with GLU 446 and GLY 379 with two H-bonds, while amino acid residues GLU 446 are positioned at a distance of H-bond with Spirotryprostatin B from *Aspergillus sydowi* (Fungi). Last but not the least, the microbial ligand Dehydrocurvularin from *Curvularia sp*. (Fungi) interacted with the target protein with residues ARG 252, ASN 262, and GLU 211 forming three H-bonds. Taken together we propose the above indicated microbial bioactive compounds as a candidate for drug for GD, thus limiting viral maturation.

Secondary metabolites of microbial origin have been proven to be an important source for new pharmaceuticals and drug lead candidates like antibacterial agents like penicillin, an antifungal drug like echinocandin B, cholesterol-lowering agent lovastatin, and more [15].

In line with our findings, the bioactive compound Lipoxazolidinone C has unusual 4-oxazolidinone heterocycle at its core, representing a wide spectrum of antibacterial and anti-microbial activity similar to those of the commercial antibiotic linezolid (Zyvox) [16]. Another study suggests that 4-oxazolidinones are valuable scaffolds of antimicrobial development [17]. Cinnamic acid and its phenolic analogs are natural substances. Isopropyl 4-hydroxycinnamate and butyl 4-hydroxycinnamate were found to have almost similar antifungal activity as commercial fungicide iprobenfos against *Pythium sp.* [18]. For decades, cinnamic acid and its derivatives have attained huge attention for their anticancer as well as antitumor potentials [19]. Similarly, cinnamic, coumaric, ferulic, and sinapic acids show inhibitory activity against several Gram-positive and Gram-negative bacteria [20] and have been found to be potential natural antifouling agents inhibiting larval settlement of *Balanus neritina* [21]. The marine natural product, marinopyrrole A has been shown to have potent antibiotic activity against Grampositive pathogens [22]. According to the data of ChEBI, the biological roles of marinopyrrole A are marine, bacterial metabolite, as well as antimicrobial, antibacterial, and antineoplastic agents. Due to the antibiotic and cytotoxicity, marinopyrrole A and its derivatives are possible for SAR studies [23]. The cultural broth of marine fungal strain from genus *Exophiala* produced new aspyrone derivatives called Chloroaspyrones A and B. Both the compounds displayed moderate to weak antibacterial activity when tested against *S. aureus* [24]. 14-hydroxyterezine is a type of diketopiperazine alkaloids, isolated from ethyl acetate of *Aspergillus sydowi*, exhibits weak cytotoxicity against human alveolar basal carcinoma A-549 cells [25]. Racemosin A is a unique bisindole alkaloid possessing a structure derived from a green alga. Studies suggest that Racemosin A significantly attenuates the Aβ25-35 induced SH-SY5Y cell damage with an increase in cell viability in a neuro-protective assay [26] and shows anti-cancer activity exhibiting a strong inhibitor against human breast cancer cell lines [27]. Apralactone A has shown moderate concentration-dependent cytotoxicity in 36 cancer cell line panels, playing an important role in the development of anticancer drugs [28]. In vitro drug susceptibilities tests and in vivo characterization in an animal model showed that LBM-415 had a good antimicrobial activity that is equivalent to the marketed antibiotic agents [29]. LBM 415 is the first peptide deformylase (PDF) inhibitor class being developed for clinical trials for oral and parenteral treatment for the respiratory tract, and skin structure infections caused by susceptible gram-positive and gram-negative organisms [30]. In an experiment, scientists isolated a novel compound named Spirotryprostatin B which inhibited the cell cycle progression of tsFT210 cells at the G2/M phase, in addition, they show cytotoxic activity on the growth of human chronic myelogenous leukemia K562 cells and human promyelocytic leukemia HL-60 cells [31]. In a recent study, Dehydrocurvularin (DCV) was revealed to have a potent irreversible inhibitor of ATP-citrate lyase (ACLY) through classical chemoproteomic profiling indicating the anti-cancer mode of action of DCV [32]. Similarly, dehydrocurvularin was found to be a fungal metabolite during the screening of fungal metabolites inhibiting TGF-β dependent signaling [33].
