Aim: To biosynthesize silver nanoparticles (AgNPs) using fungal isolates [DS-2 (Penicillium oxalicum) and DW-8 (Fusarium hainanense)] as well as their mixed cellfree filtrate (CFF) acting as a consortium (DSW-28) and their bio-potentials. Methods and Results:The fungi (DS-2 and DW-8) were harvested and CFF was prepared. CFF of each fungus and their mixture were reacted with silver nitrate solution under dark conditions for the synthesis of AgNPs. The UV-Visible spectra determined the surface plasmon resonance at 438, 441 and 437 nm for the AgNPs synthesized by DS-2, DW-8 and DSW-28, respectively. The band gap energy was found between 2.21 and 2.24 eV which depicted their ability to act as a semiconductor. The TEM imaging revealed the spherical shape and small size of AgNPs. The XRD pattern exhibited the crystalline structure corresponding to their peaks. The FTIR spectra indicate the presence of different functional groups present on the surface of AgNPs. The broad-spectrum antimicrobial activity was exhibited by AgNPs. The AgNPs also act as an effective antioxidant by depicting their radical scavenging activity against DPPH. Moreover, the AgNPs also inhibited the growth of fourth instar larvae of Aedes aegypti and Culex quinquefasciatus more efficiently in a dosedependent method. The biosynthesized AgNPs from DSW-28 showed a significant anticancer activity against MCF-7 cells. Conclusion:The silver nanoparticles synthesized by the CFF of two different fungi act synergistically in a consortium leading towards the production of silver nanoparticles with smaller size and higher bioactivity. Significance and Impact of the Study:The impressive bioactivity of the silver nanoparticles synthesized by the mixture of CFF of various fungi acting as a consortium recommends their prospective use in agriculture as well as in biomedical as an antimicrobial, antioxidant, larvicidal and anticancer agents in future.

Background: Major deaths due to colorectal cancer (CRC) arise from the metastatic dissemination of primary tumors, which is related to molecules contributing to metastatic phenotype, the pathways they control, and the genes they regulate. Purpose: To evaluate the effect of eugenol (EUG) and beta-caryophyllene (BCP) in combination with 5-fluorouracil in-vitro cytotoxic activity and in-silico method. Methods: We tested the compounds on human colorectal cancer cell line HCT116 for the combined effect of 5-FU with EUG and BCP in in-vitro MTT assay. The pharmacokinetic assessment was carried out through in-silico ADMET analysis. Compound-Disease-Target (C-D-T) network were constructed against metastatic Colorectal cancer (mCRC) from which the hub proteins were selected for molecular docking studies. Enrichment analysis for the key targets was explored for gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways involved in mCRC to explore their functional role in human body for EUG, BCP and 5-FU. Results: ADMET analysis showed that both the compounds follow the rule of five with good bioavailability thus, the compounds were found to be in the acceptable range by following drug-likeness properties. MTT assay revealed in-vitrocytotoxic effects of all three compounds and a significant reduction in IC50 values (p < 0.05) when treated the cells in combination thereby giving synergistic effects (CI < 1) represented by the Fa-CI plot. C-D-T network showed that EUG, BCP, and 5-FU target 58, 24, and 49 proteins of metastatic CRC, out of which 11 target proteins were intersected in the Venn diagram. The merged C-D-T network of these three compounds showed 84 target proteins of CRC from which 16 were selected based on their edge count which includes HSP90AA1, IGF-1R, ESR1, and CASP3. These were further screened in molecular docking which depicted that EUG, BCP, and 5-FU inhibited the C-D-T network’s core target protein HSP90AA1 (Heat shock protein-90 alpha) more effectively than any other proteins. Conclusion: Our data revealed multitarget strategy to increase the effectiveness of the drug 5-FU by reducing its dosage when combined with natural phytocomponents EUG and BCP. Here, the synergism also proved effective against mCRC.