<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Some salicylaldehyde-derived Baylis-Hillman adducts and 3-(chloromethyl)coumarins have been synthesised and evaluated <italic>in vitro</italic> for their antisickling activities. The compounds were screened for inhibitory and reversal activity against mutated haemoglobin (HbSS) in red blood cells at four different concentrations (4 mg/mL, 2 mg/mL, 1 mg/mL and 0.5 mg/mL) as a measure of their antisickling potentials. Among the synthesized compounds, 6-chloro-3-(chloromethyl)coumarin <bold>4d</bold> showed the highest inhibitory activity (83.75±1.90%), followed by 6-chlorocoumarin-3-methylsulfinic acid <bold>5d</bold> (80.90 ±0.91%) and the least was <italic>tert</italic>-butyl-3-hydroxy- 3-(2-hydroxyphenyl)-2-methylenepropanoate <bold>3a (</bold>33.33±1.86%). The results obtained from the reversal antisickling experiment showed that the percentage of sickle cells able to revert to the normal biconcave shape was dose dependent. Compound <bold>5d</bold> had the highest reversal activity (66.49±1.39%) followed by 6-bromo-3- (chloromethyl)coumarin <bold>4c</bold> (59.66±2.95) and <bold>4d</bold> (55.50±1.95%) at 4 mg/mL. Compound <bold>4c</bold> had higher reversal activity than the standard <italic>p</italic>-hydroxybenzoic acid at 2 mg/mL, 1 mg/mL and at 0.5 mg/mL. The 3-substituted coumarins <bold>4a-d</bold>, and <bold>5d</bold> had higher inhibitory antisickling activities than their Baylis-Hillman precursors <bold>3a-d</bold>. Effect of <bold>4a-d</bold> and <bold>5d</bold> on the rate of polymerization of sickle cell heamoglobin was further studied spectrophotomerically using hemolysate of HbSS. The considerable inhibitory and reversal activities of these compounds make them good candidates for further antisickling studies.</p></abstract>

Some salicylaldehyde-derived Baylis-Hillman adducts and 3-(chloromethyl)coumarins have been synthesised and evaluated in vitro for their antisickling activities. The compounds were screened for inhibitory and reversal activity against mutated haemoglobin (HbSS) in red blood cells at four different concentrations (4 mg/mL, 2 mg/mL, 1 mg/mL and 0.5 mg/mL) as a measure of their antisickling potentials. Among the synthesized compounds, 6-chloro-3-(chloromethyl)coumarin 4d showed the highest inhibitory activity (83.75±1.90%), followed by 6-chlorocoumarin-3-methylsulfinic acid 5d (80.90 ±0.91%) and the least was tert-butyl-3-hydroxy- 3-(2-hydroxyphenyl)-2-methylenepropanoate 3a (33.33±1.86%). The results obtained from the reversal antisickling experiment showed that the percentage of sickle cells able to revert to the normal biconcave shape was dose dependent. Compound 5d had the highest reversal activity (66.49±1.39%) followed by 6-bromo-3- (chloromethyl)coumarin 4c (59.66±2.95) and 4d (55.50±1.95%) at 4 mg/mL. Compound 4c had higher reversal activity than the standard p-hydroxybenzoic acid at 2 mg/mL, 1 mg/mL and at 0.5 mg/mL. The 3-substituted coumarins 4a-d, and 5d had higher inhibitory antisickling activities than their Baylis-Hillman precursors 3a-d. Effect of 4a-d and 5d on the rate of polymerization of sickle cell heamoglobin was further studied spectrophotomerically using hemolysate of HbSS. The considerable inhibitory and reversal activities of these compounds make them good candidates for further antisickling studies.

Evaluation of Some Salicylaldehyde-derived Baylis-Hillman Adducts and Coumarin Derivatives as Potential Antisickling Compounds

Department of Chemistry, Faculty of Science

Drug Research and Production Unit, Faculty of Pharmacy

Annals of Science and Technology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Some salicylaldehyde-derived Baylis-Hillman adducts and 3-(chloromethyl)coumarins have been synthesised and evaluated in vitro for their antisickling...

Evaluation of Some Salicylaldehyde-derived Baylis-Hillman Adducts and Coumarin Derivatives as Potential Antisickling Compounds

Data publikacji: 29 sie 2018

Zakres stron: 35 - 42

Otrzymano: 14 lut 2017

Przyjęty: 09 kwi 2018

DOI: https://doi.org/10.2478/ast-2018-0013

Słowa kluczowe
Antisickling Activity, Baylis-Hillman Adducts, Coumarins, HbSS Red Blood, Polymerization

© 2018 Temitope O. Olomola et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Evaluation of Some Salicylaldehyde-derived Baylis-Hillman Adducts and Coumarin Derivatives as Potential Antisickling Compounds

Data publikacji: 29 sie 2018

Zakres stron: 35 - 42

Otrzymano: 14 lut 2017

Przyjęty: 09 kwi 2018

DOI: https://doi.org/10.2478/ast-2018-0013

Słowa kluczoweAntisickling Activity, Baylis-Hillman Adducts, Coumarins, HbSS Red Blood, Polymerization

© 2018 Temitope O. Olomola et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Słowa kluczowe
Antisickling Activity, Baylis-Hillman Adducts, Coumarins, HbSS Red Blood, Polymerization