Nasim Hasan Rama

Synthesis, antioxidant activities and urease inhibition of some new 1,2,4-triazole and 1,3,4-thiadiazole derivatives

New series of 4,5-disubstituted-2,4-dihydro-3H-1,2,4-triazole-3-thiones (8a-j) and 2,5-disubstituted-1,3,4-thiadiazoles (9a-h) were synthesized by dehydrative cyclization of hydrazinecarbothioamide derivatives (7a-k) by refluxing in 4N aqueous sodium hydroxide and by overnight stirring with polyphosphoric acid, respectively. The structures of the newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR, elemental analysis and mass spectroscopic studies and the synthesized compounds were screened for their antioxidant and urease inhibition activities. N-(2,4-Dimethylphenyl)-5-(4-nitrophenyl)-1,3,4-thiadiazol-2-amine (9h) showed excellent antioxidant activity more than the standard drug whereas 4-(2,4-dimethylphenyl)-5-(3-nitrophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (8d) and 4-(2,3-dimethylphenyl)-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (8e) exhibited potent urease inhibitory activities.

Identification of Novel Urease Inhibitors by High-Throughput Virtual and in Vitro Screening

Ureases are important in both agriculture and human health. Bacterial ureases are directly involved in many farm-field problems and pathological conditions. Here, we report a structure-based virtual screening of an in-house compound bank of about 6000 molecular entities by computational docking and binding free energy calculations followed by in vitro screening. Applied protocol leads to the identification of novel urease inhibitors, which can serve as starting points for structural optimization.

Synthesis and Antimicrobial Activities of Some Isocoumarin and Dihydroisocoumarin Derivatives

A new series of the isocoumarin derivatives of ibuprofen, fluribiprofen, naproxen, valproic acid and 1-naphthoic acid have been synthesized via condensation of homophthalic acid with their respective acid chlorides. The conversion of the latter two isocoumarins into ( dl )-3,4-dihydroisocoumarins has also been achieved. Most of the synthesized compounds showed antifungal and antibacterial activities.

Synthesis, urease inhibition, antioxidant and antibacterial studies of some 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones and their 3,6-disubstituted 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole derivatives

A new series of 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones, bearing various methoxybenzyl- and methoxyphenethyl groups, was synthesized by refluxing potassium hydrazinecarbodithioate salts in dilute aqueous solution of hydrazine hydrate. These salts were formed by the reaction of acid hydrazides and carbon disulfide in methanolic potassium hydroxide solution at 0-5 °C. 4-Amino-5-aryl-3H-1,2,4-triazole-3-thiones were condensed with different substituted aromatic acids to yield 3,6-disubstituted-1,2,4-triazolo[3,4-b]1,3,4-thiadiazoles. The structures of the synthesized compounds were characterized by infrared (IR), 1H and 13C nuclear magnetic resonance (NMR), elemental analysis and mass spectrometric (MS) studies. All the synthesized compounds were screened for their urease inhibition, antioxidant and antibacterial activities. Some compounds showed excellent urease inhibition activity, more than the standard drug. Others exhibited potent antioxidant activity. All the compounds showed significant antibacterial activities as compared to the standard drug.

Synthesis, urease inhibition, antioxidant, antibacterial, and molecular docking studies of 1,3,4-oxadiazole derivatives.

A series of eighteen 1,3,4-oxadiazole derivatives have been synthesized by treating aromatic acid hydrazides with carbon disulfide in ethanolic potassium hydroxide yielding potassium salts of 1,3,4-oxadiazoles. Upon neutralization with 1 N hydrochloric acid yielded crude crystals of 1,3,4-oxadiazoles, which were purified by recrystallization in boiling methanol. The synthesized 1,3,4-oxadiazoles derivatives were evaluated in vitro for their urease inhibitory activities, most of the investigated compounds were potent inhibitors of Jack bean urease. The molecular docking studies were performed by docking them into the crystal structure of Jack bean urease to observe the mode of interaction of synthesized compounds. The synthesized compounds were also tested for antibacterial and antioxidant activities and some derivatives exhibited very promising results.

Synthesis, Acetylcholinesterase and Alkaline Phosphatase Inhibition of Some New 1,2,4-Triazole and 1,3,4-Thiadiazole Derivatives

A new series of 4,5-disubstituted-2,4-dihydro-3H-1,2,4-triazole-3-thiones (6a–s) and 2,5-disubstituted-1,3,4-thiadiazoles (7a–h) was synthesized by intramolecular dehydrocyclization of various 1,4-disubstituted thiosemicarbazide derivatives (5a–s) by refluxing in 4 N aqueous sodium hydroxide and by overnight stirring with polyphosphoric acid, respectively. The structures of these compounds were characterized by IR, 1H and 13C NMR, elemental analysis and mass spectroscopic studies. All the synthesized compounds were screened for their acetylcholinesterase and alkaline phosphatase inhibition studies. Most of the tested compounds showed promising activities, amongst them (6k) and (6q) showed excellent acetylcholinesterase inhibitory activity with IC50 0.241 ± 0.012 and 0.260 ± 0.013 µM, respectively, as compared with those of standard drug whereas the compound (6p), with IC50 0.044 ± 0.001 µM, was found to be the most potent inhibitor of alkaline phosphatase.

Chemistry of isocoumarins: synthesis and biological screenings of Homalicine and dihydrohomalicine

Total synthesis and selected biological activities of naturally occurring homalicine and (dl)-dihydrohmalicine are described.

Synthesis, herbicidal, fungicidal and insecticidal evaluation of 3-(dichlorophenyl)- isocoumarins and (±)-3-(dichlorophenyl)-3,4-dihydroisocoumarins

This is the first report showing that 3-(dichlorophenyl)isocoumarins and (±)-3,4-dihydroisocoumarins are plant and plant fungus growth inhibitors. 3-Dichlorophenylisocoumarins were synthesized by condensation of homophthalic acid with dichlorobenzoyl chlorides. The alkaline hydrolysis of these isocoumarins afforded keto acids. Racemic 3-(Dichlorophenyl)-3,4-dihydroisocoumarins were obtained by reduction of keto acids to racemic hydroxy acids, followed by cyclodehydration using acetic anhydride. The herbicidal, fungicidal and insecticidal activities of the synthesized compounds have been evaluated. Some of the synthesized compounds show excellent herbicidal and fungicidal activities but none of the synthesized compounds presented any insecticidal effects on the test insects. The findings of this study suggest that isocoumarins and related compounds may serve as lead compounds towards the design of bioactive herbicides and fungicides.

A Convenient Synthesis of 2-Arylindazol-3-Ones

Abstract The reductive cyclisation of o-nitrobenzanilides with zinc and sodium hydroxide in aqueous methanol provides a convenient source of 2-arylindazol-3-ones.

The chemistry of fungi. Part 74. Synthesis of (±)-5-butyl-6,8-dihydroxy-3-pentyl-3,4-dihydroisocoumarin

The title compound (1; R1= Bun, R2= H), which corresponds to the (+)-dihydro-derivative of fusamarin (2), a metabolite of an unidentified species of Fusarium, has been synthesised. (2-Butyl-3,5-dimethoxyphenyl)acetic acid (3; R1= OH, R2= Bun) was obtained from ethyl 3,5-dimethoxyphenylacetate by way of the corresponding 2-formyl derivative (3; R1= OEt, R2= CHO). Reaction of the acid chloride (3; R1= Cl, R2= Bun) with pentylmagnesium bromide furnished 1-(2-butyl-3,5-dimethoxyphenyl)heptan-2-one (4; Ru = Bun), which was reduced to the alcohol (5; R1= H, R2= Bun). Formylation of the acetate (5; R1= Ac, R2= Bun), followed by oxidation and hydrolysis of the ester residue, gave (±)-5-butyl-3-pentyl-6,8-dimethoxy-3,4-dihydroisocoumarin (1; R1= Bun, R2= Me), which was demethylated to (1; R1= Bun, R2= H). In model experiments (±)-6,8-dihydroxy-3-pentyl-3,4-dihydroisocoumarin (1; R1= R2= H) and related derivatives, together with associated isochromans of type (7), have been synthesised.