Synthesis of Some New Bisindole Derivatives and Their Biological Activity

Pyrrolidines are well known for their versatile pharmacological activities such as antimicrobial [1] [2] [3] [4], antitumor [5], anti HIV [6], anticonvulsant [7] [8], human melanocortin-4 receptor agonists [9], etc. Moreover, indole nucleus is an important element of many natural and synthetic molecules that covers some of the relevant and recent achievement in the biological, chemical and pharmaceutical activity of important indole derivatives [10]. In view of these observations, the intention is directed to synthesize some new bisindole derivatives of expected biological interest.


Introduction
Pyrrolidines are well known for their versatile pharmacological activities such as antimicrobial [1] [2] [3] [4], antitumor [5], anti HIV [6], anticonvulsant [7] [8], human melanocortin-4 receptor agonists [9], etc.Moreover, indole nucleus is an important element of many natural and synthetic molecules that covers some of the relevant and recent achievement in the biological, chemical and pharmaceutical activity of important indole derivatives [10].In view of these observations, the intention is directed to synthesize some new bisindole derivatives of expected biological interest.

General
All melting points are uncorrected.IR spectra were recorded (KBr) with a Perkin-Elmer 1430 spectrophotometer. 1 H NMR spectra were obtained on Varian EM 399.65 MHz equipment.MS spectra were recorded with a Jeol the MS route JMS-600 H. Substituted 1,4-diaza-1,3-butadienes (1a-f) were prepared according to known procedures by condensation of glyoxal and aromatic amines.

Antimicrobial Activity *
Antibacterial screening of compounds (3a-f) were determined by Nutrient agar well diffusion method.The tested compounds (3a-f) were dissolved in ethylene glycol to give 2% concentration.Antibacterial activity was determined according to the method reported by Bauer et al. [11] using 3 mm filter paper discs (Watmann No. 2) loaded with 10 μL of the solution under investigation (2.0%).The discs were placed on the surface of the bacterial culture, which were incubated at 30˚C.The diameter of the inhibition zone around each disc was measured (cf.Table 1).
Compound (4) was postulated as a key intermediate.The compounds produced satisfactory results for elemental and spectral analysis.

Conclusion
The title compounds are synthesized successfully through simple novel route and one pot reaction from substituted 1,4-diaza-1,3-butadienes and 1,4-naphthoquinone.These compounds also exhibited strongly to remarkable bactericidal activity against some tested bacteria.