Design, One-pot Synthesis and Biological Evaluation of Imidazo[2,1-b] [1,3,4] Thiadiazole Derivatives for their Anti- Tubercular and Anti-Fungal Activity
Abstract
In the present designed work, we have synthesized imidazo[2,1-b][1,3,4]thiadiazole derivatives (6a1-a6 to 6d1-d6) by reaction of compound 3 with appropriate α-haloaryl ketones produce substituted imidazo thiadiazole derivatives (4a-d). In the next step, these compounds (4a–d) undergoes the Vilsmeier reaction to introduce formyl group on the substituted arylimidazo[2,1-b][1,3,4]thiadiazole derivatives to form carbaldehyde derivatives (5a–d) and finally in the last step of the reaction for the synthesis of designed molecules, a one-pot synthetic procedure was used. For this, the one-pot reaction of 5a–d, thiosemicarbazide and substituted α-haloaryl ketones were reacted together in different reaction condition in ethanol solvent at an optimum temperature around 80°C produces a corresponding derivatives (6a1-a6 to 6d1-d6) with a better yield. The IR, 1H-NMR, and mass spectroscopy techniques were used to confirm the structure of final products and all synthesized molecules were tested for antiTB and anti-fungal activity. The compounds 6a1, 6a2, 6a3, 6c1, 6c6 and 6d1 with MIC 1.6-6.25 µgm/ml displayed very good antitubercular and 6a1, 6a4, 6a5, and 6d1 displayed very good antifungal activity with MIC 5 µgm/ml due to electron withdrawing groups at 4th position to both phenyl rings which are attached to the thiazole of the imidazo thiadiazole and imidazo thiadiazole ring.
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Introduction
Worldwide, Tuberculosis is utmost top ten causes of death, 1.72 million of people were died around the world in 2016, among them 0.42 million of people suffering from HIV along with TB especially in low and middle-class income countries like India, China, Indonesia, Nigeria, South Africa, Philippines, and Pakistan. The 96% of death occurred due to TB in the countries mentioned above among those India stands first with most deaths. In general, the main compliance of TB is a synergy with HIV, Multidrugresistant strain development and patient non- compliance due to MTB has made the circumstance ever more risk and it is extensively recognized that innovative intrusion tactics are required (Zheng and Blanchard, 2001). The basic imidazothiadiazole is an interesting and more demanding moiety with exciting biotic properties such as antimicrobial (Gwande et al., 1987; Desai and Baxi, 1992; Mamolo et al., 1996; Gadad et al., 2000; Alireza et al., 2003), antifungal (Alagawadi and Alegaon, 2011; Alagawadi and Alegaon, 2011), anti-tubercular (Manjoor et al., 2013; Arya et al., 1972; Gadad et al., 2004), anti-inflammatory (Labanauskas et al., 2001), antihyperlipidemic (Patel et al., 2013), antihypertensive (Turner et al., 1988; Turner et al., 1988) and anticancer (Noolvi et al., 2011; Noolvi et al., 2012; Gireesh et al., 2011; Gireesh et al., 2013; Kumar et al., 2014; Chou et al., 2003).
Conclusion
The present study on the substituted derivatives of imidazo[2,1-b][1,3,4]thiadiazole showed a moderate to finest activity against Mycobacterium tuberculosis and fungal species.
There is a scope with a slight modification on the basic moiety can produce excellent derivatives with better activity and enhanced pharmacokinetic property.