Antibacterial and In vivo Cytotoxic Activities of the Leaves of Leucas aspera

Alam, Mohammad Sayed,Saha, Sanjit,Lee, Dong-Ung 한국응용생명화학회 2014 Applied Biological Chemistry (Appl Biol Chem) Vol.57 No.5

Antimicrobial and cytotoxic activities of the leaves of Leucas aspera, a medicinal plant found in Bangladesh, were evaluated. In vitro bactericidal activity was screened against ten pathogenic or food poisoning bacteria using the disc diffusion method. In vivo cytotoxicity was examined against Artemia salina (brine shrimp nauplii). The dichloromethane fraction of the methanol extract of the leaves of Leucas aspera had strong antibacterial and cytotoxic effects, whereas the ethyl acetate fraction exhibited significant bactericidal activity against only Gram-positive bacterial strains. The active constituents, ${\alpha}$-amyrin and ${\alpha}$-tocopherol, were isolated for the first time from the dichloromethane fraction and their cytotoxic effects against A. salina were significant with $LC_{50}$ values of 241 and 195 ppm, respectively.

Cytotoxic and Antimicrobial Properties of Furoflavones and Furochalcones

( Mohammad Sayed Alam ),( Dong Ung Lee ) 한국응용생명화학회 2011 Applied Biological Chemistry (Appl Biol Chem) Vol.54 No.5

Antibacterial, antifungal, and cytotoxic activities of synthetic but naturally abundant furoflavones were evaluated, including pongaglabrone (1), pongaglabol methyl ether (2), lanceolatin B (3), pongaglabol (4), and their corresponding furochalcones (5-8) against selected bacterial and fungal strains and brine shrimp (Artemia salina) nauplii, respectively. Among the tested compounds, pongaglabrone (1) showed strong inhibition of bacterial growth against Shigella dysenteriae and Streptococcus β-haemolyticus. All furoflavones exhibited significant antibacterial activity against S.dysenteriae, Salmonella typhi, Streptococcus-β-haemolyticus, and Staphylococcus aureus, whereas the furochalcones showed selective antibacterial activity. Compound 2 exhibited the highest antifungal activity, followed by compound 1, against Aspergillus niger and Aspergillus fumigatus. Among the furochalcones tested, only compound 6 showed antifungal activity. Cytotoxicities of the synthesized compounds were compared in a short term bioassay using A. salina. Among the substances tested, compound 1 showed the highest cytotoxicity, followed by 2, 4, and 3, with LC50 values of 5.46, 8.53, 9.08, and 14.67 ppm, respectively.

Synthesis, biological evaluation, drug-likeness, and in silico screening of novel benzylidene-hydrazone analogues as small molecule anticancer agents

Mohammad Sayed Alam,Dong Ung Lee 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.2

A series of fifteen benzylidene-hydrazone analogues (3a–o), including eight new compounds, were synthesized and evaluated for their cytotoxic activities in four human cancer cell lines and for their antioxidant activities using DPPH. Of the tested compounds 3e, which possesses two methoxy substituents in its benzylidene phenyl ring, was found to be potently cytotoxic to all cancer cell lines tested with IC50 values of 0.12 (lung), 0.024 (ovarian), 0.097 (melanoma), and 0.05 lM (colon), and these IC50 values were comparable to those of the doxorubicin standard (IC50 = 0.021, 0.074, 0.001, and 0.872 lM, respectively). DPPH assay showed compounds 3f, 3i, and 3g had IC50 values of 0.60, 0.99, and 1.30 lM, respectively, which were comparable to that of ascorbic acid (IC50 = 0.87 lM). Computational parameters such as, drug-likeness, ADME properties, toxicity effects, and drug scores were evaluated, and none of the fifteen compounds violated Lipinski’s rule of five or Veber’s rule, and thus they demonstrated good drug-likeness properties. In addition, all fifteen compounds had a higher drug score than the doxorubicin and BIBR1532. In silico screening was also conducted by docking of the active compounds on the active site of telomerase reverse transcriptase catalytic subunit, an important therapeutic target of anticancer agents, to determine the probable binding properties. The total binding energies of docked compounds are correlated well with cytotoxic potencies (pIC50) against lung, ovarian, melanoma, and colon cancer cell lines indicating that the benzylidene-hydrazones could use for the development of new anticancer agents as a telomerase inhibitor.

Quantum-Chemical Studies to Approach the Antioxidant Mechanism of Nonphenolic Hydrazone Schiff Base Analogs: Synthesis, Molecular Structure, Hirshfeld and Density Functional Theory Analyses

ALAM MOHAMMAD SAYED,이동웅 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.2

In the present study, five nonphenolic (E)-N′-benzylidenebenzohydrazides including three new compounds were synthesized and evaluated for their free radical scavenging activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH). X-Ray analysis of a single crystal of (E)-N′-(4-chlorobenzylidene)benzohydrazide (3c) revealed a triclinic, space group P-1 structure with a trans configuration around the azomethine (C2N2) double bond. The three-dimensional Hirshfeld surfaces and the related two-dimensional fingerprint plots were also drawn to study the plausible intermolecular interactions. Density functional calculations of structures, electronic densities, frontier molecular orbitals modeling, and Mulliken charge analysis of all compounds were performed at the B3LYP/6-311G level of theory. Theoretical vibrational frequencies were predicted and compared with experimental values, and results supported the validity of optimized geometry of noncrystalline compounds. All synthesized compounds showed significant DPPH radical scavenging activity, although compound 3d exhibited greatest antioxidant activity with an IC50 value of 11 μM. The results of DFT analysis were used to explain the proposed antioxidant mechanism of (E)-N′-benzylidenebenzohydrazide analogs. This analysis revealed that protons attached to N, O, and C atoms possessing high negative charge are involved in the production of free radicals that scavenge DPPH. Moreover, the antioxidant activities of (E)-N′-benzylidenebenzohydrazide analogs correlated well with HOMO–LUMO energy difference of molecules.

Antibacterial and Cytotoxic Activities of Schiff Base Analogues of 4-Aminoantipyrine

ALAM MOHAMMAD SAYED,Md. Latiful Bari,이동웅 한국응용생명화학회 2014 Applied Biological Chemistry (Appl Biol Chem) Vol.57 No.5

Schiff base is the class of compounds showing widerange of biological activities having the azomethine (-N=CH-)active pharmacophore, which play major roles in their significantbio-activities. A series of Schiff base analogues of 4-aminoantipyrineanalogues have been tested for bactericidal andcytotoxic activities against selected bacterial strains and brineshrimp (Artemia salina) nauplii, respectively. Of the compoundstested, two compounds showed a good inhibition of bacterialgrowth against E. coli and C. sakazakii, whereas three compoundsdemonstrated high cytotoxicity with LC50 values of 225, 480, and581 ppm, in a short term bioassay using A. salina. Qualitativestructure-cytotoxic activity relationships were studied usingphysicochemical parameters; a good correlation between clogPand cytotoxic activity was observed.

Structure-Antimicrobial Activity Relationship of 4- or 5-Substituted 1-(2,6-Dichloro-4-trifluoromethylphenyl)-1H-1,2,3-triazole Analogues

ALAM MOHAMMAD SAYED,Yoshihisa Ozoe,Dong-Ung Lee 한국응용생명화학회 2011 Applied Biological Chemistry (Appl Biol Chem) Vol.54 No.1

A series of 1-(2,6-dichloro-4-trifluoromethylphenyl)-1H-1,2,3-triazole analogues have been tested for antimicrobial activity against thirteen bacteria and three fungi in order to observe the broad spectrum activity. Among the compounds tested, the C-4-chloropropyl derivative exhibited potent antibacterial and antifungal activities. The C-4-substituted regioisomers of 1-(2,6-dichloro-4-trifluoromethylphenyl)-1H-1,2,3-triazole exhibited moderate selectivity to broad spectrum activity, compared to that of 5-substituted regioisomers.

Antibacterial and In vivo Cytotoxic Activities of the Leaves of Leucas aspera

Mohammad Sayed Alam,Sanjit Saha,이동웅 한국응용생명화학회 2014 Applied Biological Chemistry (Appl Biol Chem) Vol.57 No.5

Antimicrobial and cytotoxic activities of the leaves ofLeucas aspera, a medicinal plant found in Bangladesh, wereevaluated. In vitro bactericidal activity was screened against tenpathogenic or food poisoning bacteria using the disc diffusionmethod. In vivo cytotoxicity was examined against Artemia salina(brine shrimp nauplii). The dichloromethane fraction of the methanolextract of the leaves of Leucas aspera had strong antibacterial andcytotoxic effects, whereas the ethyl acetate fraction exhibitedsignificant bactericidal activity against only Gram-positive bacterialstrains. The active constituents, α-amyrin and α-tocopherol, wereisolated for the first time from the dichloromethane fraction andtheir cytotoxic effects against A. salina were significant with LC50values of 241 and 195 ppm, respectively.

Cytotoxic and Antimicrobial Properties of Furoflavones and Furochalcones

ALAM MOHAMMAD SAYED,Dong-Ung Lee 한국응용생명화학회 2011 Applied Biological Chemistry (Appl Biol Chem) Vol.54 No.5

Antibacterial, antifungal, and cytotoxic activities of synthetic but naturally abundant furoflavones were evaluated, including pongaglabrone (1), pongaglabol methyl ether (2), lanceolatin B (3), pongaglabol (4), and their corresponding furochalcones (5-8) against selected bacterial and fungal strains and brine shrimp (Artemia salina) nauplii, respectively. Among the tested compounds,pongaglabrone (1) showed strong inhibition of bacterial growth against Shigella dysenteriae and Streptococcus β-haemolyticus. All furoflavones exhibited significant antibacterial activity against S.dysenteriae, Salmonella typhi, Streptococcus-β-haemolyticus, and Staphylococcus aureus, whereas the furochalcones showed selective antibacterial activity. Compound 2 exhibited the highest antifungal activity, followed by compound 1, against Aspergillus niger and Aspergillus fumigatus. Among the furochalcones tested, only compound 6 showed antifungal activity. Cytotoxicities of the synthesized compounds were compared in a short term bioassay using A. salina. Among the substances tested, compound 1 showed the highest cytotoxicity, followed by 2, 4, and 3, with LC50values of 5.46, 8.53, 9.08, and 14.67 ppm, respectively.

Biological features, drug-likeness, pharmacokinetic properties, and docking of 2-arylidenehydrazinyl-4-arylthiazole analogues

ALAM MOHAMMAD SAYED,Junaid Uddin Ahmed,이동웅 한국응용생명화학회 2016 Applied Biological Chemistry (Appl Biol Chem) Vol.59 No.2

Thiazoles are an important class of heterocyclic compounds that possess a sulfur and nitrogen containing five-membered ring, which acts as a pharmacophore, and show a wide range of complex biological activities. A series of sixteen 2-arylidenehydrazinyl-4-arylthiazole analogues (3a–p) were evaluated for cytotoxic activity against brine shrimp (Artemia salina) nauplii and their minimum inhibitory concentrations were determined against two Gram-positive (Listeriamonocytogenes and Enterococcus faecalis) and two Gram-negative bacterial strains (C.sakazakii and E. coli). Of the tested compounds, 3g demonstrated highest cytotoxicity with a LC50 value of 54 ppm followed by compound 3h(LC50 = 85 ppm), in a short-term bioassay using A. salina, whereas compound 3i exhibited the most potent antibacterial activities against L.monocytogenes, E. faecalis, and C.sakazakii with MIC values ranging from 50 to 100 μg mL−1. Compound 3g showed highest antibacterial activity against E. coli (MIC = 50 μg mL−1). In silico drug-likeness, pharmacokinetic (ADME) properties, toxicity effects, and drug scores were also evaluated, and none of the sixteen compounds were found to violate Lipiniski’s rule of five or Veber’s rule, indicating potential for development as oral drug candidates. In addition, a docking study of compound 3i into the active site of E. coli FabH receptor, an attractive target for the development of new antibacterial agents, showed it has good binding properties.

Novel Fluorescent Schiff Base Derivatives of 4-Aminoantipyrine with Large Stokes Shifts and Dual Emission Properties: Crystal Structure, Molecular Interactions, Molecular Surfaces, Conformational and DFT Analyses

Mohammad Sayed Alam,이동웅 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.10

Two novel Schiff base analogs derived from 4-aminoantipyrine, namely, (E)-4-(2-nitrobenzylideneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (3a) and (E)-4-(4-nitrobenzylideneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (3b), were synthesized using a mild and efficient method and characterized by FT-IR,1H NMR, mass spectrometry, and single-crystal X-ray diffraction studies. X-ray analysis of a single crystal of 3a revealed an orthorhombic space group P2(1)2(1)2(1) structure, with an E-configuration around the azomethine (C12N3) double bond. One unit cell was found to contain four molecules showing π−π and π−σ van der Waals stacking interactions. Plausible intermolecular interactions were analyzed using 3D Hirshfeld surfaces and the related 2D fingerprint plots. The optimized molecular structure, potential energy surface (PES) scan, vibrational frequencies, Mulliken charge distribution, molecular electrostatic potential (MEP) maps, frontier molecular orbitals (FMOs), and associated energies of 3a and 3b were calculated using density functional theory (DFT) calculations using the B3LYP method and the 6-311G(d,p) basis set. PES scans showed that the conformational energy profiles of 3a and 3b were dissimilar around the torsion angles N3–C12–C13–C14/C18 and C12–N3–C3–C2/C1 due to substituent position effects on the benzylidene phenyl ring. Mulliken charge distribution analysis revealed that O1, N1, and N3 atoms of 3a and 3b could act as electron donors and coordinate with metals, while MEP analysis showed that O1, N3, and O2–O3 are the most suitable sites for electrophilic attack. Regarding drug–receptor interactions, molecular lipophilic potential (MLP) maps demonstrated that the benzylidene phenyl ring favors lipophilic contact and the pyrazolone ring hydrophilic contact. In addition, UV–vis and fluorescence spectroscopic experiments showed that both compounds have good absorbance and fluorescent properties and large Stokes shifts. Interestingly, both compounds showed dual emission in ethanol, acetone, and diethyl ether, possibly due to conformational isomerization induced by photoexcitation.