Synthesis and Pharmacological Evaluation of Tricyclic Carbazole Annulated with Substituted Benzothiazole-2-Amine Under Microwave Irradiation
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2018, Vol 9, Issue 2
Abstract
Tricyclic carbazole nucleus is an integral part of naturally occurring alkaloids and synthetic derivatives, possessing various potential biological activities such as anticancer, antimicrobial and antiviral. Binding mechanism of carbazole with target receptor as molecule or fused molecule exhibit potential lethal effect. In the present work, development of microwave assisted organic synthesis (MAOS) methods for synthesis of a novel series of N-Mannich bases of carbazole annulled with substituted benzothiazole-2-amine with carbazole (secondary aromatic amine) and aldehyde derivatives has been presented. All the synthesized compounds were characterized by physicochemical and spectral methods viz. ultra-violet, FT-IR, 1H-NMR, Mass and elemental analysis. The newly developed MAOS method evident the improvement in percentage yield (% yield) and reaction time compared to conventional method. The synthesized compounds were screened for antibacterial (B. subtilis, S. aureus, E. coli and P. aeruginosa) and antifungal activities (A. niger and C. albicans) using impregnated paper-disc diffusion method. Compounds posses electronegative functional group at C5 and C6 position showed significant potential for antibacterial (compd. 2c and 3c) and antifungal (compd. 1b, 2b and 7b). Furthermore, in silico (PASS prediction) analysis predicts the possible mechanism of synthesized compounds could be a glycosylphosphatidylinositol phospholipase D inhibitor (antifungal action) and potassium channel blocker (antibacterial action). Tricyclic carbazole nucleus is an integral part of naturally occurring alkaloids and synthetic derivatives, possessing various biological activities such as antiviral [1] antibacterial [2] antimicrobial [3] anti-inflammatory [4] antifungal, antiprotozoological [5] antioxidant [6] antidiarrhoeal [7] anticancer [8] etc. The derivat- ization of carbazole derivatives, especially with fused heterocyclic compounds has attained a significant attention in search of newer antimicrobial molecules and anticancer with an enhanced pharmacological activity using bio-isosteric replacements [9,10]. The development of newer compounds with enhanced activity of car- bazole nucleus is constantly under investigation due to their high affinity towards DNA. This high affinity is based on their intercalation property in the minor groove of DNA, which is attributed to the secondary amine (>NH) group of carbazole moiety [11,12] In recent research, the development of N-Mannich bases of heterocyclic moieties significantly become important due to the rendering of molecule aqueous solubility when transferred to the ammonium salt [13]. The N-Man- nich bases are the compounds with powerful bond between carbon atoms having wide application to prepare diverse amino alkyl derivatives involving the condensation of active hydrogen containing molecules with aldehyde and primary or secondary amine [14]. The existing literature suggested the synthesis of N-Mannich bases derived from different heterocyclic moieties i.e. carbazole, triazole, benzimidazole possessing wide spectrum pharmacological activities [15-18]. Recently, the integration of microwave assisted organic synthesis (MAOS) in drug discovery has become an invaluable technique. Indeed, the use of microwave irradiation is simplified and improves the classical organic reactions which lead to the higher yields, cleaner reaction and shorter time of reaction [19]. Thus, based on the expectation of the wide application of carbazole nucleus and MAOS reaction, the present work employs the development of MAOS methods for the synthesis of new series of N-Mannich bases of carbazole. The developed MAOS method was compared with conventional adopted method including the percentage yield (% yield) and reaction time. MAOS reactions showed the better % yield and less reaction time. The synthesized compounds were experimentally screened for antibacterial activity against gram positive (S. aureus and B. subtilis) and gram negative (P aeruginosa and E. coli) bacteria while antifungal activity was screened against A. niger and C. albicans. Later on, the in-silico predicted biological activities were compared with experimentally performed activities.
Authors and Affiliations
Atul Sharma, Sanjit Kumar Das, Devender Pathak, Gyanendra Kumar Sharma
Keywords
Related Articles
- EP ID EP586781
- DOI 10.26717/BJSTR.2018.09.001786
- Views 140
- Downloads 0
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