Search

A facile, efficient, and convenient synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives is described using aromatic aldehydes, ethyl acetoacetate, and 2-amino benzothiazole in the presence of l-proline under solvent-free conditions. Present methodology has advantages such as short reaction time, no side products, and easy to work up. Synthesized library compounds have been evaluated for their antitumor and antimicrobial activity. Further, we have compared the experimental work with theoretical parameters using molecular property analysis to develop new ideas about the preparation of pyrimido benzothiazole derivatives for their possible application against cancer and chronic microbial diseases. It has been concluded that Petra/osiris/molinspiration (POM) analyses might prove to be a suitable method to correlate the structural features of 4H-pyrimido[2,1-b]benzothiazole derivatives with their promising combined antimicrobial/antitumor activity and may contribute to the development of novel antimicrobial and antitumor agents against drug resistance.

Series of curcumin derivatives/analogues were designed and efficient method for synthesis thereof is described. All the synthesized compounds have been screened for their cytotoxicity and evaluated their antioxidant activity. Cytotoxicity effect has been evaluated against three cell lines Hep-G2, HCT-116 and QG-56 by MTT assay method. Structure activity relationship has revealed that particularly, compound 3c, (IC50 value 6.25 μM) has shown better cytotoxicity effect against three cell lines. According to results of SAR study, it was found that 4H-pyrimido[2,1-b]benzothiazole derivatives (2e and 2f), pyrazoles (3a, 3b, 3c and 3d) benzylidenes (4d) exhibited better antioxidant activity than curcumin. A correlation of structure and activities relationship of these compounds with respect to drug score profiles and other physico-chemical properties of drugs are described and verified experimentally.

Novel KOH-loaded MgO and hydrotalcite as basic catalysts have been synthesized and were characterized by XRD, SEM and their basicity. The effect of the KOH wt%, reaction time, basicity and catalyst loading have been investigated in three-component reactions of aldehydes, 2-amino benzothiazole and 2-naphthol. The present studies showed the impact of KOH loading and reaction time. The best conversion and yield at 70 °C obtained were 93% and 88%, respectively. Hydrotalcite could be reused four times without a loss of the catalytic efficiency. Present catalytic system requires a short reaction time, is non toxic, easy to workup, has a good catalytic activity and gives a high efficiency.

A series of sixteen curcumin derivatives (CURC-D) were designed and evaluated for their antibacterial/antifungal activity. POM analyses showed that lipophilicity and presence of (X–Y) pharmacophore site (X, Y = O, N) are the major factors that governed the orientation in determining antibacterial and/antifungal activity. Furthermore, it was also found that some of the POM analyzed CURC-derivatives have a closed pharmacophore sites which might be responsible of low bioactivity. To confirm the electronic, steric, and hydrophobic requirements for future modifications, we have also carried out receptor-based electrostatic analysis. Therefore, we conclude that POM analyses may prove to be a suitable method to correlate structural features of CURC-D with their promising combined antibacterial/antifungal activity and may contribute to the development of novel antimicrobial agents against drug-resistant human pathogens.

An efficient method has been developed for the preparation of 4H-pyrimido[2,1-b]benzothiazole derivatives by the condensation of aldehydes, β-ketoester, and 2-amino benzothiazole under solvent and solvent-free conditions using various catalysts. The reaction uses benzothiazole as a new component, and good yield is obtained at 60–65°C under solvent-free conditions. Atom economies, good yield, environmentally benign, and easy to work-up are some of the important features of this protocol. The present study suggests that acetic acid and metal catalysts follow different mechanism. In acetic acid, 2-amino benzothiazole reacts with benzaldehyde, and resultant intermediate reacts with ethyl acetoacetate to give final product, whereas in the presence of metal catalysts, 2-amino benzothiazole first reacts with ethyl acetoacetate, and resultant intermediate reacts with benzaldehyde to give pyrimido[2,1-b]benzothiazole.

A novel, one-pot, simple, efficient procedure for 4H-pyrimido[2,1-b]benzothiazole (4a-h), pyrazole (6a-d) and benzylidene (7a-d) derivatives of curcumin under solvent and solvent free conditions in microwave with good yield is have been synthesized. The synthesized compounds were evaluated for their antibacterial activity against gram-positive and gram-negative bacteria viz. Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhi, Escherichia coli, Bacillus cereus and Providencia rettgeri and antifungal activity against fungi viz Aspergillus niger, Aspergillus fumigates, Aspergillus flavus. Detailed mechanistic study shows reaction proceeds through Knoevenagel type intermediate 3a which has been suggested as key intermediate for reaction (Fig. 3).

Aluminum trichloride acts as readily available, inexpensive, and efficient catalyst for one-pot three-component condensation reaction of aldehydes, dicarbonyl, and 2-amino benzothiazole under the solvent-free conditions to afford the 4H-pyrimido[2,1-b][1,3]benzothiazole derivatives 4 with good yield. The compounds synthesized in this study were evaluated for their antibacterial activities against gram-positive and gram-negative bacteria, viz., Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhi, Escherichia coli, Bacillus cereus, and Providencia rettegeri. Compounds 4c, 4d, 4f, 4g, and 4h showed their good activities against tested bacterial species. Pyrimidine derivatives 4d, 4f, and 4g have shown good antifungal activities against tested fungal strains, such as Aspergillus niger, Aspergillus fumigates, Aspergillus flavus, etc.

An efficient method has been developed for the preparation of 4H-pyrimido[2,1-b]benzothiazole derivatives by the condensation of aldehydes, β-ketoester, and 2-amino benzothiazole under solvent and solvent-free conditions using various catalysts. The reaction uses benzothiazole as a new component, and good yield is obtained at 60–65°C under solvent-free conditions. Atom economies, good yield, environmentally benign, and easy to work-up are some of the important features of this protocol. The present study suggests that acetic acid and metal catalysts follow different mechanism. In acetic acid, 2-amino benzothiazole reacts with benzaldehyde, and resultant intermediate reacts with ethyl acetoacetate to give final product, whereas in the presence of metal catalysts, 2-amino benzothiazole first reacts with ethyl acetoacetate, and resultant intermediate reacts with benzaldehyde to give pyrimido[2,1-b]benzothiazole.

A kaolin catalyzed solvent-free synthesis for new heterocyclic compounds is described. A series of heterocyclic compounds can be readily obtained using the three-component reaction of diketones, aldehydes and 2-amino benzothiazole, urea or thiourea. The mechanism of the three component kaolin catalyzed Biginelli (using urea and thiourea) and Biginelli like (using 2-amino benzothiazole) reaction has been investigated. This is the first time that we have isolated and characterized the key intermediates using 1H NMR, 13C NMR and ESI-mass spectral characterization. Imine 3 and Knoevenagel type intermediate 4 were strongly suggested as key intermediates by mechanistic study. The reaction is simple, clean and good yield is obtained within minutes.

A simple, efficient and step-economy synthesis to afford the library of 4H-pyrimido[2,1-b][1,3]benzothiazole derivatives of curcumin (4a–4h) from readily available substrates curcumin (potential biological molecule), 2-amino benzothiazole (biological active) and substituted aromatic aldehydes using novel heterogeneous calcined Mg-Al-CO3 hydrotalcite under solvent free conditions is described. The calcined hydrotalcite with an Mg/Al ratio of 3:1 derived from calcinations at 750 K was found to be a suitable catalyst that gives the highest basicity and the best catalytic activity for this reaction. The catalysts were characterized with XRD and SEM and Hammett titration method. This protocol has several advantages such as easy to work up, high activity of catalyst and reusability.

The synthesis of the 4H-pyrimido[2,1-b][1,3]benzothiazole (1a–1h), 1,2,4-triazoloquinazolines (2a,2b), octahydroquinazolinones (3a,3b) and fused thiazolo[2,3-b]quinazolinone (4a,4b) by multicomponent reactions using aldehydes, dicarbonyl and 2-amino benzothiazole/3-amino-1,2,4-triazole/urea/thiorea has been carried out in the presence of Mg–Al–CO3 and Ca–Al–CO3 hydrotalcite as a heterogeneous catalyst. Hydrotalcites need short reaction times, are non-toxic, easy to work up and reusable under solvent free conditions, hence making this process environment friendly. A detailed mechanistic study shows that the reaction using urea proceeds through imine intermediate 6. In addition, we have isolated and characterized the key intermediate of the reaction by using hydrotalcite.