Lokesh Ravi

Binding mode of dihydroquinazolinones with lysozyme and its antifungal activity against Aspergillus species.

Aspergillosis is one of the infectious fungal diseases affecting mainly the immunocompromised patients. The scarcity of the antifungal targets has identified the importance of N-myristoyl transferase (NMT) in the regulation of fungal pathway. The dihydroquinazolinone molecules were designed on the basis of fragments responsible for binding with the target enzyme. The aryl halide, 1(a-g), aryl boronic acid and potassium carbonate were heated together in water and dioxane mixture to yield new CC bond formation in dihydroquinazolinone. The bis(triphenylphosphine)palladium(II) dichloride was used as catalyst for the CC bond formation. The synthesized series were screened for their in vitro antifungal activity against Aspergillus niger and Aspergillus fumigatus. The binding interactions of the active compound with lysozyme were explored using multiple spectroscopic studies. Molecular docking study of dihydroquinazolinones with the enzyme revealed the information regarding various binding forces involved in the interaction.

Natural alkaloid Luotonin A and its affixed acceptor molecules: Serum albumin binding studies

Effective interaction of natural alkaloid Luotonin A (L) and its affixed acceptor molecules 1 and 2 with donor molecule as Bovine serum albumin (BSA) at various pH (4.0, 7.4 and 10.0) medium have been demonstrated using various conventional spectroscopic techniques. These analyses provide some valuable features on the interaction between BSA and acceptor molecules (L, 1 and 2). From the absorption and fluorescence spectral titration studies, the formation of ground-state complexes between the acceptor molecules (L, 1 and 2) and the BSA have been confirmed. The results of the afore titrations analysis reveal that, the strong binding of receptor 1 with BSA (Kapp 5.68×104M-1; KSV 1.86×106Lmol-1; Ka 6.42×105Lmol-1; Kass 8.09×106M-1; ΔG -33.35kJ/mol) at physiological pH medium (7.4) than other receptor molecules 2 and L. The Förster resonance energy transfer (FRET) efficiency between the tryptophan (Trp) residues of BSA and acceptor molecules L, 1 and 2 during the interaction, are 28.85, 85.24 and 53.25 % respectively. The superior binding efficacy of acceptor 1 at physiological pH condition has been further confirmed by FT-IR and Raman spectral analysis methods. Moreover, theoretical docking studies of acceptors L, 1 and 2 towards HSA have been demonstrated to differentiate their binding behaviours. It reveals that, acceptor 1 has the strongest binding ability with HSA through two hydrogen bonding and the Atomic contact energy (ACE) value of -483.96kcal/mol.

Antibacterial and Antifungal Potential of Marine Streptomyces sp. VITAK1 derived Novel Compound Pyrrolidinyl-Hexadeca-Heptaenone by in Silico docking Analysis

The rapid emergence of antibiotic resistance by pathogenic bacteria underlines the need for new antibacterial agents from natural sources. With those objective marine actinomycetes derived novel compound was screened for antibacterial and antifungal activity by in-silico molecular docking studies. Twelve actinomycetes were isolated from marine soil samples collected from Andaman and Nicobar Islands of India. All the isolates were screened for antibacterial activity against selected ATCC bacterial pathogens and the isolate VITAK1 showed significant antibacterial activity. It was characterized by molecular taxonomic and phylogeny and identified as Streptomyces species and designated as Streptomyces sp. VITAK1. The 16S rRNA partial gene sequence (1296 nucleotides) of VITAK1 was submitted to the GenBank under the accession ID: KF478916. Bioactivity-guided extraction, purification and characterization of the compound through GC-MS, FT-IR and NMR (H1and C13) lead to the identification of compound, [(3E, 5E, 7E, 9E, 11E, 13E, 15E)-16-(pyrrolidin-1-yl) hexadeca-3, 5, 7, 9, 11, 13, 15-heptaen-2-one] with a molecular weight of 295.41 Da and molecular formula C20H25NO. The extracted compound was found to be anovelbased on PUBCHEM and SciFinderdatabase. The compound exhibited the least free binding energy of -8.8 Kcal/mol with the fungal drug target enzyme N-myristoyl transferase and also showed the free binding energy of -8.14 Kcal/mol with folate synthesising enzyme dihydropteroate synthase. The results of the in Silico studies suggest that the novel compound PHDH exhibit antibacterialactivity by inhibiting folate synthesis in the target bacteria and antifungal activity by inhibiting the ergosterol synthesis.

A review on bioactive secondary metabolites reported from actinomycetes isolated from marine soil samples of indian peninsula

The aim of this review is to give an update on actinobacteria derived bioactive secondary metabolites reported from Indian Peninsula. Several research groups in India are working on actinomycetes diversityand focusing more on antimicrobial, antiparasitic, anticancer activity and enzymes produced by these species. Several reports are available on multiple biological activitiesof culture filtrate/crude extracts obtained from actinomycetes isolates. Bioactivity guided extraction, purification andcompound identification has yielded several novel compounds. Scalable production of bioactive compounds from potential actinomycetes is under different phases of clinical trials for drug development as antibiotics worldwide. Currently actinomycetes research is more intense and more predominant not only in India but throughout the world due to its well-known ability to produce novel antibiotics and new chemical entities. The demand for new antibiotics from marine actinomycetes to overcome microbial drug resistance and to develop a new anticancer drug leads is ever persistent. Several novel antibiotics and anticancer metabolites are already been reported from actinomycetes in the recent past. In this review the bioactive compounds reported from marine actinomycetes species isolated from samples collected at various locations of Indian Peninsula has been reviewed.. The focus of the present review is to summarize the antimicrobial (antibacterial-ESBL, MRSA, VRE, antidermatophytic and anticandidal) and anticancer secondary metabolites reported from actinomycetes.

Crystal structure, optical properties, DFT analysis of new morpholine based Schiff base ligands and their copper(II) complexes: DNA, protein docking analyses, antibacterial study and anticancer evaluation

New morpholine derived Schiff base ligands (HL1 and HL2) and their Cu(II) complexes [Cu(L1)2] (1) and [Cu(L2)2] (2) have been synthesized and characterized by 1H NMR, IR, UV-Vis, EPR studies and cyclic voltammetric analyses. Single crystal X-ray crystallography studies confirm the structure of newly synthesized Schiff base ligands HL1and HL2. The ground state electronic structures of Cu(II) complexes 1 and 2 have been investigated by DFT/B3LYP theoretical analysis with 6-31G (d,p) and LANL2DZ basis set. The affinity towards DNA and protein molecules have been evaluated using computational docking analysis and complex 2 expose significant binding ability with DNA as well as protein due to its towering hydrophobicity. Consequently, complex 2 reveals superior antibacterial activity against some bacterial species besides anticancer activity on human breast cancer (MCF-7) cells than complex 1 and Schiff base ligands (HL1 and HL2). These preliminary investigations strongly recommended that complex 2 can be used as a better antibacterial plus anticancer agent.