Molecular docking study of naturallyoccurring compounds as inhibitors of N-myristoyl transferase towards antifungal agents discovery

Abstract

Fungal infections currently remain as a common problem in public health. Actually, drug discovery programs are oriented to the searching for lead structures. Virtual screening and molecular docking constitute great alternatives in order to find hit compounds. Novel infection targets can also be defined and employed together with molecular docking tools in drug discovery programs. Thus, thirty-two natural compounds were docked within the active site of N-myristoyl transferase (NMT) as antifungal enzyme target. From tested compounds, alkaloids, flavonoids, xanthones, and quinones exhibited strongest mean interaction with NMT than terpenoids, coumarins and phenolics. Particularly, affinities for one aporphine alkaloid, a prenylated flavonoid and two xanthones resulted to be comparable with that of previously reported synthetic inhibitor. Several hydrophobic and polar contacts were demonstrated by comparing different computational tools. The present results let to establish three possible lead structures to develop antifungal drugs although subsequent SAR analyses are still required.

Potential inhibitory activity of phytoconstituents against black fungus: In silico ADMET, molecular docking and MD simulation studies

“…Evidence from several in vivo , in vitro , and animal studies suggests that phenolic compounds such as phenols, coumarins, flavonoids, tannins, quinines, xanthones and stilbenoids from natural sources have antifungal properties and, it’s also shown that their activity is mainly due to the site (s) and the number of hydroxyl groups in a compound are assumed to be related to their relative toxicity to microorganisms. As previously stated, increasing toxicity is related to more hydroxylation [80] , [108] , [113] . Moreover, phenol compounds with higher degree of oxidation were shown more inhibitory activities [131] .…”

“…Studies also indicated that the antifungal activities of flavonoids like isopiscerythrone, allolicoisoflavone A, piscisoflavones A, B and C, licoflavone A, papyriflavonol A, quercetin, hesperidin, neohesperidin and naringin, because of their ability to bind to extracellular and soluble proteins, as well as to bind to fungal cell walls. The more lipophilic nature of flavonoids may also account for the disrupted fungal membranes [69] , [80] , [90] , [96] , [99] , [107] . A large number of studies have established that terpenoids such as estragole, encelin and panicutine exhibit antifungal activity.…”

“…Limonin is the first isolated limonoids found in medicinal plants, such as citrus, neem, tulsi and licorice. Limonoids have been identified as having various biological properties including antibacterial, antifungal, antiviral, antimalarial, and anticancer [72] , [78] , [80] , [106] . Saponins are steroidal or terpenoid-based glycosides with surface-active properties such as saponin and sapindoside B. CAY-1, a triterpene saponin from the Capsicum frutescens, was reported to be potent against 16 different fungal strains, including C. neoformans , A. fumigatus , and Candida spp .…”

“…A list of 158 bioactive compounds was collected from various herbals that were reported as anti-fungal agents [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] , [80] , [81] , [82] , [83] , [84] , [85] , [86] , [87] , [88] , [89] , [90] , [91] , [92] , [93] , [94] , [95] , [96] , [97] , [98] , [99] , [100] , [101] , [102] , [103] , [104] , [105] , [106] , [107] , [108] , [109] , [110] , [111] , [112] , [113] . The 3D structure of phytochemicals were downloaded from Pubchem database ( https://pubchem.ncbi.nlm.nih.gov/ ) in SDF format.…”

Repurposing of Modified Alpidem and Propoxyphene to Cure AURKA, BCAS1, GNAS and MLH1 Gene Mutations in Colorectal Cancer

“…However; Virtual screening and molecular docking constitutes extraordinary options so as to discover hit compounds. Novel disease targets can likewise be characterized and utilized together with molecular docking tools used in drug discovery programs [16]. The fewer side effects and docking results of both modified Alpidem and Propoxyphene suggests that both the drugs can be used to cure mutations of genes in colorectal cancer as both modified drugs have fewer side effects and toxicity values.…”