Molecular docking and dynamics simulation study of quinones and pyrones from Alternaria solani and Alternaria alternata with HSP90: an important therapeutic target of cancer.

Although cancer continues to be one of the world's major causes of death, current cancer drugs have many serious side effects. There remains a need for new anticancer agents to overcome these shortcomings. Alternaria is one of the most widespread fungal genera, many species of which produce several classes of metabolites with potential polypharmacological activities. A few quinones and pyrones from Alternaria spp. have proven to exert cytotoxic effects against certain cancer cell lines, but their molecular mode of action is not known. The current study aimed to investigate the potential mechanisms that underlie the anticancer activity of a few selected quinones and pyrones from Alternaria solani and Alternaria alternata by molecular docking and dynamic simulation approaches. The selected metabolites were screened for their binding affinity to Heat shock protein 90 (HSP90), which is a known anticancer drug target. Molecular docking studies have revealed that Macrosporin, Altersolanol B, Fonsecin, and Neoaltenuene have good binding affinities with the target protein and the stabilities of the formed complexes were evaluated through molecular dynamics simulations. By analyzing the Root Mean Square Distance (RMSD), Root Mean Square Fluctuation (RMSF), and Principal Component Analysis (PCA) plots obtained from molecular dynamics simulations, this study shows that the complexes of all 4 lead molecules with target protein are stable over a 100 ns period. Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations were used to compute the binding free energies. The lead molecules were studied using in-silico analysis to determine their drug-likeness based on their Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) and physicochemical properties. The results demonstrate that Macrosporin, Fonsecin, and Neoaltenuene could become promising anticancer molecules that target HSP90.Communicated by Ramaswamy H. Sarma.

Diversity of arbuscular mycorrhizal fungi in irrigated and non-irrigated fields of southern Karnataka, India.

The two different agro-ecosystems were selected to study the spore density, species abundance, and diversity of arbuscular mycorrhizal fungi (AMF) in irrigated (Mandya district) and non-irrigated (Hassan district) agricultural fields in southern Karnataka region, India. A total of 22 AMF species were recorded during the study. Out of which 13 sp. were of Glomus, 4 sp. of Acaulospora, 1 sp. of Cetraspora, 1 sp. of Dentiscutata and 3 sp. of Gigaspora. The difference in species richness of AMF species in irrigated fields ranged from 5-12 sp. as compared to non-irrigated fields (5-11 sp.) and the difference may be attributed to the nutritional status of the soil. We also assumed that lower AMF colonization and abundance would be affected by water stress. Highest spore number and percent colonization of AM fungi were recorded in irrigated sites, showing 356-748 spore density and 70-92% colonization. Whereas, in non-irrigated sites, 174-341 spore density and 40-72% colonization was recorded. Different agro-climatic conditions like irrigation, soil pH, soil organic carbon, phosphorous correlated with the abundance and colonization of AM fungi.

Infectivity and efficacy of Glomus aggregatum and growth response of Cajanus cajan (L.) Millsp. in flyash amended sterile soil.

In the present investigation a pot culture experiment was conducted using sterile, phosphorus deficient soil to study the effect of flyash at 3 different concentrations (10g, 20g and 30g flyash/kg soil) on the infectivity and effectiveness of VAM fungus Glomus aggregatum in pigeonpea (Cajanus cajan (L.) Millsp.) cv Maruti. The flyash amendment in soil at all the 3 different concentrations was found to affect significantly the intensity of VAM fungal colonization inside the plant roots and also suppressed the formation of VAM fungal structure (vesicles and arbuscules) completely at higher concentration (30g flyash/kg soil). The response of the pigeonpea plants, as judged by their higher and dry weight, under the influence of flyash amendment in VAM fungus infested soils was found to be considerably less (though not significant enough) when compared to the control plants (without flyash) that have otherwise shown significant increase in growth over the plants without Glomus aggregatum inoculation. However, flyash amendment without VAM inoculation was also found to enhance the growth of plants as compared to control plants (without flyash and VAM inoculum).