Molecular Docking of Nimbolide Extracted from Leaves of Azadirachta indica with Protein Targets to Confirm the Antifungal, Antibacterial and Insecticidal Activity.

Nimbolide, a tetranortriterpenoid (limonoid) compound isolated from the leaves of Azadirachta indica, was screened both in vitro and in silico for its antimicrobial activity against Fusarium oxysporum f. sp. cubense, Macrophomina phaseolina, Pythium aphanidermatum, Xanthomonas oryzae pv. oryzae, and insecticidal activity against Plutella xylostella. Nimbolide exhibited a concentration-dependent, broad spectrum of antimicrobial and insecticidal activity. P. aphanidermatum (82.77%) was more highly inhibited than F. oxysporum f. sp. cubense (64.46%) and M. phaseolina (43.33%). The bacterium X. oryzae pv. oryzae forms an inhibition zone of about 20.20 mm, and P. xylostella showed about 66.66% mortality against nimbolide. The affinity of nimbolide for different protein targets in bacteria, fungi, and insects was validated by in silico approaches. The 3D structure of chosen protein molecules was built by homology modelling in the SWISS-MODEL server, and molecular docking was performed with the SwissDock server. Docking of homology-modelled protein structures shows most of the chosen target proteins have a higher affinity for the furan ring of nimbolide. Additionally, the stability of the best-docked protein-ligand complex was confirmed using molecular dynamic simulation. Thus, the present in vitro and in silico studies confirm the bioactivity of nimbolide and provide a strong basis for the formulation of nimbolide-based biological pesticides. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01104-6.

Anticancer Potential of Hydroxychavicol Derived from Piper betle L: An in Silico and Cytotoxicity Study.

Piper betle L. is a popular medicinal plant in Asia, and extracts of the plant leaf are used for several therapeutics. It is known for its rich source of phenolic compounds, including hydroxychavicol. Hydroxychavicol is an allylbenzene that has gained much attention due to its anticancer properties. The current study quantified and purified hydroxychavicol from P. betle L. and predicted its anticancer competence through in silico and cytotoxicity studies. Leaf samples of 22 P. betle L. accessions from different locations of Tamil Nadu, India, were analyzed using reverse phase-high performance liquid chromatography for quantification of hydroxychavicol. The highest quantity of hydroxychavicol was obtained from the accession BV22 (89.2%). Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of hydroxychavicol using SwissADME satisfied the physicochemical property guidelines of Lipinski's Rule of Five, ensuring its drug-likeness behavior. Molecular docking studies confirmed the interaction of hydroxychavicol with all 16 tested cancer targets. In Vitro MTT assay of hydroxychavicol in bone cancer cell lines (MG63) also demonstrated the anticancer competency, indicating the requirement to formulate the molecule as a drug in treating various types of cancers.

Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics.

The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates. The heterogeneous solid state catalyst (Fe (III) Y-Zeolite) could effectively catalyze the reaction to obtain the product with high yield and short reaction time. The synthesized compounds (5a-5p) were analyzed by NMR, FTIR and HRMS analysis. Compound 5c was confirmed by single crystal XRD studies. All the compounds were biologically evaluated for their potential inhibitory effect on anticancer (MCF-7, Hep-2) and microbial (MRSA, MTCC 201 and FRCA) activities. Among the compounds 5i exhibited the highest levels of inhibitory activity against both MCF-7, Hep-2 cell lines. Furthermore, the compound 5i (BPP) was evaluated for DNA fragmentation, flow cytometry studies and cytotoxicity against MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. In addition, molecular docking (PDB ID: 1T46) studies were performed to predict the binding affinity of ligand with receptor. Moreover, the synthesized BPP compound was loaded in to the PHB-PCL nanofibrous scaffold to check the cytotoxicity against the MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. The in vitro apoptotic potential of the PHB-PCL-BPP nanofibrous scaffold was assessed against MCF-7, Hep-2 cancerous cells and fibroblast cells at 12, 24 and 48h respectively. The nanofibrous scaffold with BPP can induce apoptosis and also suppress the proliferation of cancerous cells. We anticipate that our results can provide better potential research in nanomaterial based cancer research.

Insect antifeedant and growth regulating activities of salannobutyrolactone and desacetylsalannobutyrolactone.

Salannobutyrolactone and its deacetylderivative were tested for insect antifeedant and growth regulatory activities against the tobacco cutworm, Spodoptera litura. Salannobutyrolactone was the most effective antifeedant. Desacetylsalannobutyrolactone increased larval duration and larval mortality.