Effect of Methoxy and Lipophilic Prenyl Substituents on Structure Activity Relationship of Some Synthesized Hydroxychalcones; Determined by Antimicrobial, Antioxidant and Cytotoxic Activity

Abstract

Natural chalcones and their derivatives, plant pigments are abundantly present in fem to higher plants especially in different parts of edible plants. They are belonging to flavonoid family and also considered to be main precursors in the biosynthesis of flavones, isoflavones and other biologically essential heterocycles. Flavonoids are the most common naturally occurring antioxidants and found ubiquitously in plants as pigments for flower coloration, in fruits and vegetables and play an ecological role in nature. A series of 2'-hydroxychalcones and their derivatives are found to have potential therapeutic agents against bacterial diseases. Chalcones are 1, 3- diphenyl-2-propene-1-one, in which two aromatic rings are linked by a three carbon a, ð€€“-unsaturated carbonyl system (-CO-CH=CH-). These possess conjugated double bonds and a completely delocalized n-electron system on both benzene rings. Molecules possessing such system have relatively low redox potentials and have a greater probability of undergoing electron transfer reactions. During the last sixty years synthetic as well as isolation works on the chalcones are being done throughout the world. They have been demonstrated to possess unique templates associated with very diverse application mainly biological and pharmacological activities such as antibacterial, antiviral, antioxidant, anti-inflammatory, antimutagenic, antiallergic, antiviral, antineoplastic, anti-thrombotic and vasodilatory activities and inhibitory activities in several enzymes. Structure activity relationship (SAR) is also an important factor which has aroused considerable interest to the chemist. Different functional groups which are attached to the benzene ring of chalcones can be varied to enhance activity. Chalcones and its derivatives are still an object of sustained interest thus the present study has been extended by synthesizing eight substituted chalcones; 2' -hydroxychalcone (3a), 2' -hydroxy -4 -methoxychalcone (3b), 2' -hydroxy - 2, 4, 5 - trimethoxychalcone (3c), 2', 5' - dihydroxy - 2, 4, 6 -trimethoxychalcone (3d), 4 - hydroxy - 3', 4', 5' - trimethoxychalcone (3e), 2' - hydroxy - 3' - C - prenylchalcone (4a), 2' - hydroxy - 5' - C -prenylchalcone (4b), 2', 5' - dihydroxy - 2, 4, 6 - trimethoxy - 3' - C -prenylchalcone (4c) based on Claisen-Schimdt condensation method from substituted benzaldehyde and acetophenone in good yield. They have been characterized by spectral data. The potency of the development of new antibiotic or chemotherapeutic agents is highly based on in vitro antimicrobial screening. The synthesized chalcones (3a-3e, 4a-4c) were screened in vitro for their antibacterial activity against four pathogenic bacteria viz. Bacillus caerius (G+, B1 ), Staphylococcus aureus (G+, B2), Eschericia coli (G-, B3), Agrobacterium Species (G-, B4). The primary assay was performed by disc diffusion technique to classify the microorganism susceptible as well as resistant towards particular compounds. The bioactivity is expressed by the diameter of zone of inhibition in mm. Synthesized chalcones 3d, 3b, 3b, 4c in 250 µg/disc showed very high activity against B1 (3 8), B2 ( 40), B3 (30), B4 ( 40) respectively comparing to those of the standard drug ( ciprofloxacin, C-50). The rest of the chalcones showed moderately good activity in different condition. In addition the synthesized chalcones (3a-3e, 4a-4c) were evaluated for in vitro antioxidant activity using diphenylpicrylhydrazyl (DPPH) model. Observation for antioxidant activity is expressed in terms of percent scavenging of DPPH radical and the inhibitory concentration 50% (IC50) is lowest for structure 3d, 0.923 (µg/mL) at DPPH cone. 0.02% indicating highest activity. The compound 3d contains two phenolic -OH group and suppose to produce phenoxide free radical easily and stabilized by electronic group methoxy occupied ortho and para position of aromatic ring attached to benzaldehyde part. Other structures showed good antioxidant activity as compared to the standard, ascorbic acid,