A new progestin from fungal transformation of norethisterone and its comparative antimicrobial studies.

Fungal transformation of a norethisterone (17α-ethynylestra-4-en-17ß-ol-3-one) (1) by using Macrophomina phaseolina and Paecilomyces variotii was studied. A new metabolite, 17α-hydroxymethyl-androst-4-en-11ß-ol-3-one-17ß-acetate (2) with novel changes and a known metabolite, 17α-ethynylestradiol (3) were obtained from 1 by using M. phaseolina and P. variotii, respectively. Based on various spectroscopic techniques, the structures of both metabolites were characterized. The antimicrobial activities of 1-3 were also evaluated. Compound 1 was found to be moderately active against Salmonella paratyphi while 1-3 were almost inactive against other microorganisms.

Multi-activity tetracoordinated pallado-oxadiazole thiones as anti-inflammatory, anti-Alzheimer, and anti-microbial agents: Structure, stability and bioactivity comparison with pallado-hydrazides.

Herein, we report a comparative study based on structure, thermal and solution stability, and biopotency against lipoxygenase (LOX), butyrylcholinesterase (BChE) and microbes for Pd(II) compounds of N,O,S bearing 5-(C5H4XR)-1,3,4-oxadiazole-2-thiones (L') of type [PdL'Cl2] (P'n) and N,O bearing respective hydrazides (L) of type trans-[PdL2Cl2] (Pn) {X = C, R = 4-I, 2-Br, 4-NO2, 3-NO2, 2-Cl, 3-Cl (n = 1-6, serially); X = N (n = 7)}. Spectral techniques (IR, EI-MS, NMR) and physicochemical evaluations successfully characterized the new compounds. The L' behaved as bidentate S-N donors bonded through exocyclic sulfur and N-3' nitrogen, while L acted as amino N donors. UV-vis (solution speciation) and thermal degradation profiles consistently confirmed the greater stability for P'n than Pn compounds. These compounds manifested varying degree in vitro potential to inhibit LOX, BChE and several bacteria and fungi, affected mainly by Pd(II) presence, M-L binding mode, nature and position of R, or halo groups electronegativity. Molecular docking with human 5-LOX and BChE further validated the respective experimental inhibition findings and explored several putative mechanistic interactions (H-bonding, π-stacking, π-alkyl, π-S, etc.) at the enzyme active sites. Pn generally offered superior antimicrobial and anti-LOX (anti-inflammatory) potential than respective P'n compounds, with P3/P'5, P(2,3,7)/P'3, and P6 being comparable, better and equivalent to ampicillin, nystatin and baicalein, the reference antibacterial, antifungal and anti-LOX drugs, respectively. Contrarily, the anti-BChE activity of P'n was found better than Pn compounds, showing P'2/P1 as the most promising anti-Alzheimer drug candidates. This study bares important structural and mechanistic aspects in optimizing antimicrobial, anti-inflammatory and anti-Alzheimer activities, highlighting some potential future pallado-drug candidates.

1,1'-Carbonyldiimidazole (CDI) Mediated Facile Synthesis, Structural Characterization, Antimicrobial Activity, and in-silico Studies of Coumarin- 3-carboxamide Derivatives.

BACKGROUND: Despite the availability of a variety of antibacterial agents, re-emergence of pathogenic bacteria is still a serious medical concern. So, identification of new, safer, and selective antibacterial agents is the key interest in the medicinal chemistry research. METHOD: To explore the antimicrobial activity of coumarin-3-carboxamides for a range of bacterial and fungal strains, twenty eight derivatives were synthesized by the reaction of coumarin-3-carboxylic acid with a variety of aniline derivatives in the presence of 1,1'-carbonyldiimidazole (CDI). All compounds were structurally characterized by different spectroscopic techniques EI-MS, HREI-MS, 1H-NMR, 13C-NMR, and evaluated for antimicrobial activities (antibacterial and antifungal). RESULTS: A number of compounds showed good to weak antibacterial activity against various strains of Gram-positive and Gram-negative bacteria. Amongst them, compound 28 displayed noticeable inhibition against five strains of Gram-positive (Bacillus subtilis, Corynebacterium xerosis, Staphylococcus aureus, Streptococcus faecalis, and MRSA) and four strains of Gram-negative bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter aerogene, and Shigella dysenteria). However, none of the compounds showed antifungal activity against tested fungi. MIC values were determined for most of the active compounds 2, 15, and 28 against particular bacterial cultures. In silico studies were performed on the most active compound 28 in order to specify and verify the target for antibacterial activity of synthetic coumarin-3-carboxamide derivatives. The cytotoxicity of these compounds on mammalian cells is unknown yet but we are planning to carry out research on the cytotoxic aspect of these compounds in future. CONCLUSION: The newly identified compounds may serve as lead molecules for the future research regarding the identification of new antibacterial agents.

Synthesis of novel bisindolylmethane Schiff bases and their antibacterial activity.

In an effort to develop new antibacterial drugs, some novel bisindolylmethane derivatives containing Schiff base moieties were prepared and screened for their antibacterial activity. The synthesis of the bisindolylmethane Schiff base derivatives 3-26 was carried out in three steps. First, the nitro group of 3,3'-((4-nitrophenyl)-methylene)bis(1H-indole) (1) was reduced to give the amino substituted bisindolylmethane 2 without affecting the unsaturation of the bisindolylmethane moiety using nickel boride in situ generated. Reduction of compound 1 using various catalysts showed that combination of sodium borohydride and nickel acetate provides the highest yield for compound 2. Bisindolylmethane Schiff base derivatives were synthesized by coupling various benzaldehydes with amino substituted bisindolylmethane 2. All synthesized compounds were characterized by various spectroscopic methods. The bisindolylmethane Schiff base derivatives were evaluated against selected Gram-positive and Gram-negative bacterial strains. Derivatives having halogen and nitro substituent display weak to moderate antibacterial activity against Salmonella typhi, S. paratyphi A and S. paratyphi B.

Antimycobacterial and antioxidant activities of reserpine and its derivatives.

In view of the attributed medicinal properties of reserpine, a number of acyl reserpine derivatives were prepared and tested for antimycobacterial activity against Mycobacterium tuberculosis, strain H(37)Rv and antioxidant activities. The results indicated that in the case of antimycobacterial activity, 10 out of 18 derivatives caused more inhibition than that caused by reserpine itself. The results of antioxidant activity revealed that acylation in benzene ring of reserpine decreases the percentage inhibition of DPPH in all the derivatives compared to the parent compound.

Antimicrobial activity of the methanolic bark extract of Holarrhena pubescens (Buch. Ham), its fractions and the pure compound conessine.

The antimicrobial activity of the methanolic extract of the bark of Holarrhena pubescens, its fractions, and conessine, a steroidal alkaloid, was determined against various bacteria and fungi using the agar diffusion method. They were all found to possess significant activity against some of the bacteria tested. The alkaloidal fraction and conessine also exhibited marginal activity against some of the fungi tested. The minimum inhibitory concentration (MIC) value of conessine was determined against various bacteria, and the highest activity was seen against Micrococcus luteus ATCC 9341 (MIC: 15.6 µg per disc).

New antimicrobial alkaloids from the roots of Polyalthia longifolia var. pendula.

Bioassay-guided isolation studies on the root extract of Polyalthia longifolia var. pendula possessing significant antibacterial activity led to the isolation of three new alkaloids pendulamine A (1), pendulamine B (2) and penduline (3) along with stigmasterol 3-O-beta-D-glucoside, allantoin, the known diterpenoid kolavenic acid, and the azafluorene alkaloid isoursuline. The structures of these compounds have been elucidated with the help of spectroscopic studies including 2D NMR experiments. Compounds 1 and 2, which are the only protoberberine alkaloids having a monosubstituted A ring with a hydroxy group at C-3, were found to be the active antibacterial principles of the roots. Their MIC values ranged between 0.02-20 microg against the tested bacteria.