http://ir.lib.ruh.ac.lk/handle/iruor/7384 2026-05-12T14:34:21Z http://ir.lib.ruh.ac.lk/handle/iruor/9034 In silico study for prediction of novel bioactivities of the endophytic fungal alkaloid, mycoleptodiscin B for human targets. Deshapriya, U.S.; Dinuka, D.L.S.; Ratnaweera, P.B.; Ratnaweera, C.N. Mycoleptodiscin B is a natural product extracted from the endophytic fungus Mycoleptodiscus sp. found in Sri Lanka and Panama with experimentally unexplored activities for human targets. In this study, a computational methodology was applied to determine druggable targets of mycoleptodiscin B. According to the computational toxicity and pharmacokinetics assessment, mycoleptodiscin B was proven to be a suitable drug candidate. Druggable targets for this compound, aromatase, acidic plasma glycoprotein and androgen receptor, were predicted using reverse docking. A two-step validation of those targets was performed using conventional molecular docking and molecular dynamic (MD) simulations, resulting in aromatase being determined as the potential therapeutic target. Based on molecular mechanics/Generalized Born Surface Area (GBSA) free energies and ligand stability inside the active site cavity during its 120 ns MD run, it can be concluded that mycoleptodiscin B is a potent aromatase inhibitor and could be subjected to further in vitro and in vivo experiments in the drug development pipeline. Consequently, natural product chemists can quickly identify the hidden medicinal properties of their miracle compounds using the computational approach applied in this research. 2021-01-01T00:00:00Z http://ir.lib.ruh.ac.lk/handle/iruor/9033 Isolation and structure of the anti, anti isomer and a DFT study of it and the syn, anti isomer of bis (tricarbonylchromium) dibenzo-[a, e] cyclooctatetraene. Bandara, N.; Ratnaweera, C.N.; Gwaltney, S.R.; Henry, W.P. When dibenzo[a,e]cyclooctatetraene and hexacarbonylchromium are refluxed in di-n-butyl ether /THF for an extended period, both the syn,anti and anti,anti isomers of the bis tricarbonylchromium complex are obtained. After separation by column chromatography, the syn,anti:anti,anti isomer ratio is approximately 12:1. The anti,anti arrangement of the Cr(CO)3 groups was verified by X-ray crystallographic structure determination. The orientations of the two tricarbonylchromium tripods relative to the 1,2-disubstituted arene rings differ. One is exo staggered while the other is eclipsed. Intermolecular C-H···O hydrogen bonding is prevalent in the crystal and is reminiscent of the syn,anti isomer. A dimeric motif in the solid resulting from C-H···π interactions is observed. DFT calculations on both isomers confirms that the syn,anti isomer is favored. The preferred orientation for the anti Cr(CO)3 groups in both cases is exo staggered. However, the barrier to rotation is low, allowing hydrogen bonding to readily overcome this barrier and control the orientation of the tripod. While thermodynamic consideration support the preference for the syn,anti isomer, kinetic factors may also be important as this isomer would be formed preferentially due to steric inhibition of the diene coordination site by the mononuclear anti isomer. The stabilization of the syn,anti isomer occurs by an electrostatic attraction of the syn carbonyl groups with the anti Cr(CO)3-coordinated arene carbon atoms. A reexamination of the structural parameters verifies nonbonded carbon-oxygen distances less than the sum of the van der Waals radii in the syn,anti isomer. A search of the Cambridge Structural Database results in a significant number of interactions of this nature for arenetricarbonylchromium complexes. 2013-06-29T00:00:00Z