Ali Mohammed Malla

SiO2–H3BO3 promoted solvent-free, green and sustainable synthesis of bioactive 1-substituted-1H-tetrazole analogues

In the present study, a focused library of multi functionalized 1-substituted-1H-tetrazole analogues 4(a–o) were synthesized, which were typically accessed via a facile, solvent-free and green synthetic protocol. The reaction involves expeditious reusable catalyst (SiO2–H3BO3) promoted condensation between a variety of heterocyclic/aromatic amines, sodium azide and triethyl ortho-formate, eliminating the use of an environmentally toxic solvent. This new eco-friendly and sustainable protocol resulted in a remarkable enhancement in the synthetic efficiency (90–97%, yield) with high purity. This silica–boric acid catalyst is air and water stable and easy to prepare from cheap silica and boric acid. The present methodology is a green protocol offering several advantages such as an excellent yield of products, a simple operational procedure, minimizing production of chemical wastes, mild reaction conditions, a shorter reaction profile, easy preparation of the catalyst and its recyclability up to five cycles without any appreciable loss in catalytic activity. The optimization conditions achieved in the present study revealed that 2.5 mol% of the SiO2–H3BO3 catalyst under solvent-free conditions at 90 °C are the best suited conditions for the synthesis of tetrazole derivatives in excellent yields. The present protocol is applicable to a broader substrate scope (electron-rich and electron-deficient). Compounds possessing a nicotinic acid nucleus (4e, 4f, 4g) displayed strongest inhibition against AChE with IC50 values of 0.43 μM, 0.21 μM and 0.26 μM, respectively. The results revealed that the electronic effect of substituents inflicts a prominent effect on AChE activity.

Synthesis, characterization, DNA-binding studies and acetylcholinesterase inhibition activity of new 3-formyl chromone derivatives.

A series of new substituted 3-formyl chromone derivatives (4-6) were synthesized by one step reaction methodology by knoevenagel condensation, structurally similar to known bisintercalators. The new compounds were characterized by IR, (1)H NMR, (13)C NMR, MS and analytical data. The in vitro DNA binding profile of compounds (4-6) was carried out by absorption, fluorescence and viscosity measurements. It was found that synthesized compounds, especially compound 6 (evident from binding constant value) bind strongly with calf thymus DNA, presumably via an intercalation mode. Additionally, molecular docking studies of compounds (4-6) were carried out with B-DNA (PDBID: 1BNA) which revealed that partial intercalative mode of mechanism is operational in synthesized compounds (4-6) with CT-DNA. The binding constants evaluated from fluorescence spectroscopy of compounds with CT-DNA follows the order compound 6>compound 5>compound 4. All the compounds (4-6) were screened for acetylcholinesterase inhibition assay. It can be inferred from data, that compound (6) showed potent AChE inhibition having IC50=0.27μM, almost in vicinity to reference drug Tacrine (IC50=0.19μM).

Two new phenolic compounds from Ficus rumphii and their antiproliferative activity

Two new compounds 2 and 4, along with two known compounds 1 and 3, were isolated for the first time from 95% ethanolic extract of the leaves of Ficus rumphii. Their structures were elucidated on the basis of chemical and physical evidences (elemental analysis, UV, IR, 1H NMR, 13C NMR and mass spectra) and comparison with the literature compounds. Structural authentication of compound 4 was further validated by single-crystal X-ray analysis and DFT calculations. The compounds 1–4 were screened for in vitro cytotoxicity against cancer and non-cancer cells and also tested for genotoxicity (comet assay). Compounds 2 and 4 displayed significant activity against HL-60 with IC50 values of 3.3 and 2.3 μM, respectively. The results revealed that compound 4 has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.

[Et3NH][HSO4]-catalyzed eco-friendly and expeditious synthesis of thiazolidine and oxazolidine derivatives

The present study reports a facile and green approach for the synthesis of thiazolidine/oxazolidine derivatives 4(a–u) in excellent yields (92–98%) with high purity. The protocol involves a one-pot three-component reaction of substituted 1,3-diketones 1(a–g), cyanates 2(a–c) and ethylchloroacetate (3) in ionic liquid [Et3NH][HSO4] under solvent-free conditions. The notable feature of this pathway is that the ionic liquid possesses both catalytic as well as medium engineering capability in this protocol. Use of [Et3NH][HSO4] as a catalyst and an environmentally benign solvent eliminates the need for a volatile organic solvent and additional catalyst. This ionic liquid is air and water stable and easy to prepare from cheap amine and acid. The present synthetic route is a green protocol offering several advantages, such as excellent yield of products, mild reaction conditions, minimizing chemical waste, shorter reaction time, simple operational procedure, easy preparation of the catalyst and its recyclability up to five cycles without any noticeable loss in catalytic activity. The protocol is applicable to a broad substrate scope. The optimization of conditions carried out in the present study revealed that 20 mol% of ionic liquid catalyst under solvent-free conditions at 120 °C are the best reaction parameters for the synthesis of thiazolidine/oxazolidine derivatives in excellent yields.

[Et3NH][HSO4]-mediated functionalization of hippuric acid: an unprecedented approach to 4-arylidene-2-phenyl-5(4H)-oxazolones

A facile, green and stereoselective approach for the synthesis of azlactones/oxazolones 3(a–q) has been developed. The protocol involves reaction of hippuric acid and substituted heterocyclic/aromatic aldehydes in ionic liquid [Et3NH][HSO4] to yield the desired 4-arylidene-2-phenyl-5(4H)-oxazolones in excellent yields (94–97%) with a high degree of purity. The remarkable feature of this pathway is that the ionic liquid eliminates the use of toxic and expensive acetic anhydride and is endowed with catalytic and medium engineering ability. This eco-friendly approach improved synthetic efficiency (94–97% yield), minimizing the production of chemical waste without using highly toxic reagents for the synthesis and more notably, it promoted the selectivity for Z-azlactones/oxazolones. Density functional theory (DFT) calculations revealed that the Z-isomer of compound 3a is stabilised by 2.32 kcal mol−1 more than the E-isomer. This synthetic scheme possesses diverse applicability and is compatible to a range of functional groups (electron donating/electron withdrawing).

Solvent-free, [Et3NH][HSO4] catalyzed facile synthesis of hydrazone derivatives

In the present study, a library of hydrazone analogues 2(a–j) and 4(a–e) were synthesized, which were typically accessed via a solvent-free facile nucleophilic addition between hydrazine hydrate and appropriately substituted aromatic aldehydes 1(a–j) and 3-formylchromones 3(a–e). The molecular structure of compound (2f) was well supported by single crystal X-ray crystallographic analysis and also verified by DFT calculations. This new synthetic, eco-friendly, sustainable protocol resulted in a remarkable improvement in the synthetic efficiency (90–98% yield), high purity, using [Et3NH][HSO4] as a catalyst and an environmentally benign solvent eliminating the need for a volatile organic solvent and additional catalyst. This ionic liquid is air and water stable and easy to prepare from cheap amine and acid. The present methodology is a green protocol offering several advantages such as, excellent yield of products, minimizing production of chemical wastes, shorter reaction profile, mild reaction conditions, simple operational procedure, easy preparation of catalyst and its recyclability up to five cycles without any appreciable loss in catalytic activity. The optimization conditions carried out in the present study revealed that 20 mol% of ionic liquid catalyst under solvent-free condition at 120 °C are the best conditions for the synthesis of hydrazone derivatives in excellent yields.

Stereoselective synthesis of Z-acrylonitrile derivatives: catalytic and acetylcholinesterase inhibition studies

In the present study, a focused library of (Z)-acrylonitrile analogues (library A & B) were synthesized, which were typically accessed via a facile Knoevenagel condensation between p-nitrophenylacetonitrile and appropriately substituted aromatic aldehydes (1a–i) and 3-formyl chromones (3a–c). This new synthetic eco-friendly approach resulted in a remarkable improvement in the synthetic efficiency (83–92% yield), high purity, minimizing the production of chemical wastes without using highly toxic reagents for the synthesis and, more notably, it improved the selectivity for (Z)-acrylonitrile derivatives. By performing DFT calculations, it was found that the (Z)-isomer of compound 2b is stabilized by 2.61 kcal mol−1 more than the (E)-isomer. All of the compounds were tested for acetylcholinesterase (AChE) inhibition. Compounds 2a and 4c, displayed the strongest inhibition, with IC50 values of 0.20 μM and 0.22 μM respectively. The methoxy group at the para-position of phenyl ring A was found to be essential for AChE inhibition.

An SiO2/ZnBr2 mediated expeditious approach to 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one derivatives in water under microwave irradiation

A new one-pot three-component green approach has been developed for the synthesis of a series of pyrazolone derivatives 2(a–s) from differently substituted aromatic aldehydes, ethylacetoacetate and phenylhydrazine/2,4-dinitrophenylhydrazine in excellent yields (94–98%), employing SiO2/ZnBr2 as a recyclable Lewis acid catalyst in water under microwave heating. The molecular structure of compounds 2a and 2d were well supported by single crystal X-ray crystallographic analysis. The present protocol bears a wide substrate tolerance and is believed to be more practical, efficient, eco-friendly and compatible as compared to existing methods.

Synthesis, bioassay, crystal structure and ab initio studies of Erlenmeyer azlactones.

Several 4-arylidene-2-phenyl-5(4H)-azlactones have been synthesized via Erlenmeyer method. The synthesized compounds have been characterized on the basis of systematic spectral studies (IR, (1)H NMR, (13)C NMR, and MS). The compound (4Z)-4-(3,5-dimethoxybenzylidene)-2-phenyl-1,3-oxazol-5(4H)-one, C(18)H(15)NO(4), (5), crystallizes in the orthorhombic system, space group P2(1)2(1)2(1), with a=5.6793(3) Å, b=15.2038(7) Å, c=17.6919(10) Å, Mr=309.31, V=1527.64(14) Å(3), Z=4 and R=0.0547. The compound (4Z)-2-phenyl-4-(3,4,5-trimethoxybenzylidene)-1,3-oxazol-5(4H)-one, C(19)H(17)NO(5), (6) crystallizes in triclinic geometry with space group P-1, having unit cell parameters a=7.3814(3) Å, b=8.1446(3) Å, c=13.9845(5) Å, α=86.918(3), β=83.314(2), γ=82.462(3), Mr=339.34, V=827.16(5) Å(3), Z=2 and R=0.0433. The DFT calculations of compounds (5) and (6) have been carried out to ascertain the stability of Z-conformer. The in vitro antimicrobial activity of all the compounds (1-6) was evaluated by the disk diffusion method against gram +ve and gram -ve microorganism and fungal strains. The MIC of the synthesized compounds was determined by agar well diffusion method in 96-well microtiter plate. All the synthesized compounds were also screened for their free radical scavenging activity by DPPH method.

Acetylcholinesterase and Cytotoxic Activity of Chemical Constituents of Clutia lanceolata Leaves and its Molecular Docking Study

Phytochemical investigations of the ethanolic extract of leaves of Clutia lanceolata (Family: Euphorbiaceae) resulted in the isolation of four compounds viz. 3,4-dihydroxy-2-methylbenzoic acid (1), 2,2′-dihydroxy-1,1′-binaphthyl (2), 1,3,8-trihydroxy-6-methylanthracene-9,10-dione (3) and 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one (4). Although all the isolated compounds were known but this was the first report from this plant source. Their structures were established on the basis of chemical and physical evidences viz. elemental analysis, FT-IR, 1H-NMR, 13C-NMR and mass spectral analysis. Structure of compound 2 and 4 was further authenticated by single-crystal X-ray analysis and density functional theory calculations. The isolated compounds (1–4) were screened for AChE enzyme inhibition assay in which compound 3 and 4 were found to be more potent AChE inhibitor. Molecular docking study of potent AChE inhibitor was performed to find the probable binding mode of the compounds into the active site of receptor. Moreover, the isolated compounds were also screened for in vivo cytotoxicity by brine shrimp lethality assay.Graphical Abstract