Synthesis, in vitro antiproliferative activity, antioxidant activity and molecular modeling studies of new carbazole Mannich bases
- 248 Downloads
A new class of carbazole Mannich bases were synthesized from 4-hydroxycarbazole by reacting with aromatic aldehydes and cyclic amines under mild reaction conditions in good yields. The method does not require column chromatographic purification for isolation of the products. The synthetic potential of these carbazole Mannich bases is exemplified by the ortho-quinone methide formation and subsequent in situ trapping with active methylene compounds bearing a cyano group to construct biologically active pyrano[3,2-c]carbazoles. Further, all the synthesized Mannich bases were tested for their in vitro antiproliferative activity against three cancer cell lines (Hela, MDA-MB-231, and HepG2). The results indicated that these compounds showed selective cytotoxicity against Hela cells. In addition, the synthesized carbazole Mannich bases were also screened for their scavenging activity of the 2,2-diphenyl-1-picrylhydrazyl radical and most of the compounds showed very good antioxidant activity. In silico molecular docking study of synthesized carbazole Mannich bases against colchicine binding site of the tubulin polymer was investigated.
KeywordsMannich bases 4-Hydroxycarbazole Ortho-quinone methide Pyrano[3,2-c]carbazoles Antioxidant activity Molecular docking
P. Narayana Reddy thanks to DST-SERB, India for a Start-Up Research Grant., P. Padmaja thankful to DST, India for Inspire Faculty Fellowship.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- Gul HI, Gul M, Erciyas E (2002) Syntheses and stability studies of some mannich bases of acetophenonnes and evaluation of their cytotoxicity against jurkat cells. Arzneim Forsch 52:628–635Google Scholar
- Gul M, Mete E, Atalay E, Arik M, Gul HI (2009) Cytotoxicity of 1-aryl-3-buttylamino-1-propanone hydrochlorides against jurkat and L6 cells. Arzneim Forsch 59:364–369Google Scholar
- Indumathi T, Ahamed VSJ, Moon S, Fronczek FR, Prasad KJR (2011) l-Proline anchored multicomponent synthesis of novel pyrido[2,3-a]carbazoles: investigation of in vitro antimicrobial, antioxidant, cytotoxicity and structure–activity relationship studies. Eur J Med Chem 46(11):5580–5590CrossRefPubMedGoogle Scholar
- Knolker HJ, Reddy KR (2008) The Alkaloids. In: Cordell GA (ed) Chemistry and biology. Academica Press, Amsterdam, voi. 65, p 1–430Google Scholar
- Lee CM, Plattner JJ, Ours CW, Horrom BW, Smital JR, Martin YC, Pernet AG, Bunnell PR, El Masry SE, Dodge PW (1984) [[(Aminomethyl)aryl]oxy]acetic acid esters. A new class of high ceiling diuretics. 1. Effects of nitrogen and aromatic nuclear substitution. J Med Chem 27(12):1579–1587CrossRefPubMedGoogle Scholar
- Muthumani P, Neckmohammed MR, Venkataraman S, Chidambaranathan N, Devi P, Suresh Kumar CA (2010) Synthesis and evaluation of anticonvulsant and antimicrobial activities of some mannich bases of substituted aminophenol and acetophenone. Int J Pharm Biomed Res 1(3):78–86Google Scholar
- Padmaja P, Rao GK, Indrasena A, Reddy BVS, Patel N, Shaik AB, Reddy N, Dubey PK, Bhadra MP (2015) Synthesis and biological evaluation of novel pyrano[3,2-c]carbazole derivatrives as anti-tumor agents including apoptosis via tubulin polymerization inhibition. Org Biomol Chem 13(5):1404–1414CrossRefPubMedGoogle Scholar
- Rokita SE (2009) Quinone Methides. Reactive Intermediates in Chemistry and Biology, Vol. 1, Wiley: Hoboken, NJGoogle Scholar
- Selvakumar V, Duraipandi S, Devdas S (2011) Synthesis and psychorpharmacological activities of some succinimide mannich bases. J Pharm Res 4:3168–3170Google Scholar
- Takeuchi T, Oishi S, Watanabe T, Ohno H, Sawada J, Matsuno K, Asai A, Asada N, Kitaura K, Fujii N (2011) Structure–activity relationships of carboline and carbazole derivatives as a novel class of ATP-competitive kinesin spindle protein inhibitors. J Med Chem 54(13):4839–4846CrossRefPubMedGoogle Scholar
- Xu Z, Li Y, Xiang Q, Pei Z, Liu X, Lu B, Chen L, Wang G, Pang J, Lin Y (2010) Design and synthesis of novel xyloketal derivatives and their vasorelaxing activities in rat thoracic aorta and angiogenic activities in zebrafish angiogenesis screen. J Med Chem 53(12):4642–4653CrossRefPubMedGoogle Scholar