Synthesis and Pharmacological Evaluation of Nitrogen Heterocycles with Special Emphasis on Quinoline Analogues and Isolation and Characterization of the Constituents of Nicandra physalodes

Abstract

newline ix newlineABSTRACT newlinePART-A newlineAim: The aim of present work was design, synthesis and pharmacological evaluation of novel five membered nitrogen heterocycles as anticancer and antimicrobial agents. newlineMethods: Twenty napthylpropiophenones and their pyrazoline analogues were synthesized starting from heterocyclic benzaldehyde with electron withdrawing and electron releasing groups. Compounds were purified and melting point, Rf values were determined. The structures were characterized using various spectroscopic techniques. The synthesized compounds were screened for antimicrobial and cytotoxic activities in-vitro. To understand the structure activity relationship (SAR) in-silico studies were carried out at colchicine binding site of and#945;-and#946; tubulin (PDB-1SA0). newlineResults:The results from antimicrobial and cytotoxic activities revealed that the compounds possessing electron releasing groups and rigidity in the structure showed significant growth inhibitory activity against all the tested organisms and cancer cell lines. Molecular modelling studies matched well with the in-vitro cytotoxic activity; therefore it may act as microtubule inhibitors. newlineConclusion: The naphthalene moiety with rigidity at and#945;,and#946; carbonyl system may be referred as potent synthone. Presence of electron releasing groups at para position on phenyl ring in a molecule potentiates the anticancer and antimicrobial activity which was further supported by docking studies. newlineKeywords: Napthylpropiophenones, cytotoxic activity, antimicrobial activity, pyrazoline analogues, nitrogen heterocycles, colchicine. newlinex newlinePART-B newlineAim:The aim of present work was biological evaluation of the constituents of Nicandra physalodes against cancer and microbes in-vitro. newlineMethods:The leaves of Nicandra physalodes were collected, dried and coarsely powdered. Extraction, fractionation, TLC followed by repeated column chromatography was carried out to isolate the phytoconstituents. Extracts, fractions and isolated compound were screened for antimicrobial and cytotoxic activities in-vitro. newlineResults: The phytochemical investigation showed that the plant contains alkaloids, steroids, tannins, flavonoids, carbohydrates. Among all the fractions dichloromethane (A) (non-alkaloidal) fraction showed significant inhibition against three different cancer cell lines. The compound SU-PY-NP-01 isolated from dichloromethane fraction showed significant cytotoxic activity against lung cancer (A549) and skin cancer (A431) cell lines. newlineConclusion: The plant Nicandra physalodes is a rich source of potent bioactive leads akin to steroidal components (withanolides) which may be responsible for growth inhibitory activity of non-alkaloidal fraction. The isolated steroidal compound (SU-PY-NP-01) may be referred as a withanolide from N. physalodes having significant cytotoxic activity. newlineKeywords: Nicandra physalodes, cytotoxic activity, antimicrobial activity, withanolides, bioactive.