Modulation of medicinal molecules (atenolol, gabapentin, nitrofurazone, secnidazole, zuclopenthixol,) and study of chemical constituents of cassia absus and pseudocalymma elegans

Abstract

The present thesis is divided in two parts. Both parts have their own compound numbering although each chapter has separate references. Part A The first part deals with structure modifications of medicinal molecules atenolol, gabapentin, nitrofurazone, secnidazole, and zuclopenthixol which consist of five chapters (1-5) Chapter-1 describes the synthesis of twenty-three new thiourea derivatives of atenolol (1-23). All these derivatives have exhibited urease and α-glucosidase enzyme inhibitory activities. Molecular docking studies have been performed for all the derivatives. Compounds 1, 3, 8, and 17 are found to be the most active compounds as compared to atenolol and standard thiourea for urease enzymes inhibiton; their binding sites are also reported. Compunds 2, 8, 12, and 19 are the most active compounds as compared to atenolol and standard acarbose; also their binding sites are reported. Chapter-2 describes the synthesis of twenty-one new synthetic thiourea deriavtives of gabapentin (24-44) which are active for α, β-glucosidase enzyme inhibition. Compounds 29, 33, 36, and 38 are the most active as compared to gabapentin and standard acarbose and their binding site are determined through molecular docking study. Chapter-3 describes the synthesis of twenty N-arylated/alkylated derivatives of nitrofurazone (45- 54) out of which fourteen are newly synthesized. All derivatives have exhibited moderate to good antimicrobial activities as compared to nitrofurazone. These derivatives (45-54) also possess good inhitbion against α, β-glucosidase enzymes. Compounds 46, 50, 54, and 63 are the most active as compared to parent molecule nitrofurazone and standard acarbose. Molecular docking study is performed and binding site is reported. Chapter-4 describes the synthesis of nine secnidazole-sulfonate (65-73) out of which six are newly synthesized. Antimicrobial activity and cyclic voltammetric study was performed for these compounds (65-73). Out of nine secnidazole-sulfonate compound 65-68, and 72 were obtained in cyrstaline form and their XRD analysis has been carried out. Chapter-5 describes the stability issues of zuclopenthixol decanoate. In this chapter, zuclopenthixol decanoate is synthesized and its stability issues has been discussed. x Part B The second part is based on chemical characterization of pure natural compounds and biological activities of Cassia absus Linn. and Pseudocalymma elegans Vell. which is described in two chapters (6-7). Chapter-6 describes the chemical constituents of Cassia absus Linn. Two pure compunds raffinose (1) and maltose (2) are isolated through column chromatography while sixty-nine compounds (3-70) have been identified through GC/GC-MS analysis. Methanolic extract of C. absus and its hexane: ethyl acetate, ethyl acetate and methanol fractions possess significant antioxidant activity. Anthelminthic activity is performed in which ethyl acetate fraction at higher concentration (100 mg/mL) exhibited paralytic effect, much earlier than standard piperazine citrate and the death time has been reduced as compared to standard piperazine citrate against Pheretima posthuma earthworm. Methanolic extract and fractions have exhibited moderate to good antibacterial potential while highest potential exhibited by methanolic extract. GC/GC-MS analysis and anthelminthic activity is reported first time from C.absus. Chapter-7 describes the chemical constituents of Pseudocalymma elegans. Seven pure chemical constituents 3,4-dimethoxy benzoic acid (71), α-amyrin (72), ursolic acid (73), β-amyrin (74), 3,5- dimethoxy-4-hydroxy-benzoic acid (76), quinic acid (75), and 7,4’-dihydroxy isoflavone-8-C-βglucopyranoside (77) are obtained. Sixty-three chemical constituent (78-140) from non-polar to moderate polar fractions of P. elegans have been identified through GC/GC-MS analysis. Evaluation of antioxidant and antimicrobial activities of hexane, dichloromethane, ethyl acetate, and methanolic extracts of young leaves of P. elegans have been done. All extracts and fractions have exhibited antioxidant activity however among all these, the methanolic extract showed potent activity in comparison to standards (ascorbic acid and BHT). The ethyl acetate extract exhibited excellent activities against few bacteria and some fungi as compared to the standard drugs ceftriaxone (3rdgeneration cephalosporin) and nystatin, respectively. All of these isolated (71-77) and identified compounds (78-140) as well as biological activities are reported very first time from this source.