Synthesis, antifungal and anti-hiv activities of new heterocyclic compounds
Thiophene chalcones, pyrazolines and 1,5-benzodiazepines are important heterocyclic compounds which show broad spectrum of biological activities. Three series of heterocyclic chalcones and their N-acetylated pyrazoline derivatives have been synthesized in low to good yields. The first step in this s...
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my-utm-ep.810232019-07-24T03:06:02Z Synthesis, antifungal and anti-hiv activities of new heterocyclic compounds 2019-02 Al-Maqtari, Helmi Mohammed AbdulGhani QD Chemistry Thiophene chalcones, pyrazolines and 1,5-benzodiazepines are important heterocyclic compounds which show broad spectrum of biological activities. Three series of heterocyclic chalcones and their N-acetylated pyrazoline derivatives have been synthesized in low to good yields. The first step in this study is the synthesis of 3-acetyl-2,5-dichlorothiophene and 2-acetyl-5-chlorothiophene as heterocyclic ketones using Friedel-Crafts acylation. All thiophene chalcones were synthesized in three separate reactions by Claisen-Schmidt reaction of substituted thiophene aldehydes with ketones. Several acetophenone derivatives (series 2 and 3) were produced by cyclization reaction using hydrazine hydrate to form new and known N-acetylated pyrazoline derivatives. A series of substituted 1,5-benzodiazepines were synthesized in moderate to good yields. 4-Methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one was synthesized as starting material by reacting ortho phenylenediamine and crotonic acid in the presence of toluene. Cyclization of the starting material with appropriate acid chlorides, unsubstituted and five types of groups (fluoro, chloro, bromo, methyl and methoxy) attached at ortho, para and meta position of phenyl ring in the presence of triethylamine and anhydrous tetrahydrofuran have furnished substituted 1,5-benzodiazepines. The structures of the compounds were confirmed by infrared (IR), 1H NMR and 13C NMR (1D and 2D) nuclear magnetic resonance spectroscopies. Compounds of series 2 and 3 were tested for their antifungal activities against two types of pathogenic strains, namely Candida albicansa and Aspergillus niger with fluconazole as standard drug. The results for series 2 showed that the presence of bromo and methoxy substitution at para position on phenyl ring in chalcone and pyrazoline, respectively, resulted in significant enhancement in potency against both tested fungal strains with MIC value of ＞64 µg/mL. Compound carrying para fluoro on phenyl ring in pyrazoline derivatives exhibited the highest potency with MIC value of ＞32 µg/mL and 64 µg/mL against C. albicans and A.niger, respectively, among the series 3. The anti-HIV-1 RT assay of substituted 1,5-benzodiazepines (series 4) showed that the presence of chloro substitution at meta and ortho position inhibited the activity of HIV-1 RT with IC50 values 6.87 and 8.62 µM, respectively. 2019-02 Thesis http://eprints.utm.my/id/eprint/81023/ http://eprints.utm.my/id/eprint/81023/1/HelmiMohammedAbdulGhaniPFS2019.pdf application/pdf en public http://dms.library.utm.my:8080/vital/access/manager/Repository/vital:125085 phd doctoral Universiti Teknologi Malaysia, Faculty of Science Faculty of Science |
| institution |
Universiti Teknologi Malaysia |
| collection |
UTM Institutional Repository |
| language |
English |
| topic |
QD Chemistry |
| spellingShingle |
QD Chemistry Al-Maqtari, Helmi Mohammed AbdulGhani Synthesis, antifungal and anti-hiv activities of new heterocyclic compounds |
| description |
Thiophene chalcones, pyrazolines and 1,5-benzodiazepines are important heterocyclic compounds which show broad spectrum of biological activities. Three series of heterocyclic chalcones and their N-acetylated pyrazoline derivatives have been synthesized in low to good yields. The first step in this study is the synthesis of 3-acetyl-2,5-dichlorothiophene and 2-acetyl-5-chlorothiophene as heterocyclic ketones using Friedel-Crafts acylation. All thiophene chalcones were synthesized in three separate reactions by Claisen-Schmidt reaction of substituted thiophene aldehydes with ketones. Several acetophenone derivatives (series 2 and 3) were produced by cyclization reaction using hydrazine hydrate to form new and known N-acetylated pyrazoline derivatives. A series of substituted 1,5-benzodiazepines were synthesized in moderate to good yields. 4-Methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one was synthesized as starting material by reacting ortho phenylenediamine and crotonic acid in the presence of toluene. Cyclization of the starting material with appropriate acid chlorides, unsubstituted and five types of groups (fluoro, chloro, bromo, methyl and methoxy) attached at ortho, para and meta position of phenyl ring in the presence of triethylamine and anhydrous tetrahydrofuran have furnished substituted 1,5-benzodiazepines. The structures of the compounds were confirmed by infrared (IR), 1H NMR and 13C NMR (1D and 2D) nuclear magnetic resonance spectroscopies. Compounds of series 2 and 3 were tested for their antifungal activities against two types of pathogenic strains, namely Candida albicansa and Aspergillus niger with fluconazole as standard drug. The results for series 2 showed that the presence of bromo and methoxy substitution at para position on phenyl ring in chalcone and pyrazoline, respectively, resulted in significant enhancement in potency against both tested fungal strains with MIC value of ＞64 µg/mL. Compound carrying para fluoro on phenyl ring in pyrazoline derivatives exhibited the highest potency with MIC value of ＞32 µg/mL and 64 µg/mL against C. albicans and A.niger, respectively, among the series 3. The anti-HIV-1 RT assay of substituted 1,5-benzodiazepines (series 4) showed that the presence of chloro substitution at meta and ortho position inhibited the activity of HIV-1 RT with IC50 values 6.87 and 8.62 µM, respectively. |
| format |
Thesis |
| qualification_name |
Doctor of Philosophy (PhD.) |
| qualification_level |
Doctorate |
| author |
Al-Maqtari, Helmi Mohammed AbdulGhani |
| author_facet |
Al-Maqtari, Helmi Mohammed AbdulGhani |
| author_sort |
Al-Maqtari, Helmi Mohammed AbdulGhani |
| title |
Synthesis, antifungal and anti-hiv activities of new heterocyclic compounds |
| title_short |
Synthesis, antifungal and anti-hiv activities of new heterocyclic compounds |
| title_full |
Synthesis, antifungal and anti-hiv activities of new heterocyclic compounds |
| title_fullStr |
Synthesis, antifungal and anti-hiv activities of new heterocyclic compounds |
| title_full_unstemmed |
Synthesis, antifungal and anti-hiv activities of new heterocyclic compounds |
| title_sort |
synthesis, antifungal and anti-hiv activities of new heterocyclic compounds |
| granting_institution |
Universiti Teknologi Malaysia, Faculty of Science |
| granting_department |
Faculty of Science |
| publishDate |
2019 |
| url |
http://eprints.utm.my/id/eprint/81023/1/HelmiMohammedAbdulGhaniPFS2019.pdf |
| _version_ |
1747818294374563840 |