4 Challenge and Response A Case Study of Benazir Bhutto’s Twin Prime Ministerships

Benazir Bhutto happened to be the first constitutionally chosen female leader of any Muslim country in Modern times. She ascended to office amid the legacy of General Zia-ul-Haq’s regime and civil-military bureaucracy that prompted diverse deterrence for her governments and abstained her from the application of her constitutional power. The essence of challenges was mostly political, but the grounds that created these abysses were political and gender partiality. Based on the above discourse, this article attempts to underline the torments confronted by Benazir being the new chapter in our political society. This is the empirical account of Benazir’s twin governments grounded on the views of important politicians who sight and accompanied her in her journey of power. To ponder the reasons that refrained Benazir from having true legal authority the study is divided into the following parts: (1) Challenge and response encountered by Benazir in the first tenure of her Prime Ministership (1988-90), (2) Challenge and response encountered by Benazir in the second tenure of her Prime Ministership (1993-1996). The PPP government had made some new political strides in general, but it was persistently controlled by the army. In the first government, the brass leadership and opposition and in later government civil-military bureaucracy and opposition impaired the democratic traditions. However, amid all this Benazir succeeded to do some pragmatic politics and defying the anti-PPP mindset.

Dihydropyrimidines As Potential Drug Candidates, Design, Synthesis, Bioevaluation and Computational Studies

Present work refers to the design, synthesis, bioevaluation and computational studies of multifunctionalized dihydropyrimidines (DHPMs) known to possess immense pharmacological activities. A series of DHPM derivatives were synthesized by different strategies. In the first strategy, one pot Biginelli reaction was carried out using three building blocks (i.e. aryl aldehydes, 1,3-dicarbonyl compounds and diamino compounds). Hence three different types of DHPMs namely 4-aryl-3,4- dihydropyrimidine-2-ones (1-44), 4-aryl-3,4-dihydropyrimidine-2-thiones (45-69) and 2-amino-1,4-DHPMs (70-79) were synthesized. Through this strategy diversity was introduced at N1, C2, C4, C5 and C6 positions of pyrimidine nucleus. Moreover, keeping in view the difficulties during the synthesis of DHPM via Biginelli three component reaction, the conditions were optimized by doing these reactions through different modes such as sonication, microwave irradiation, as well as through conventional heating. Excellent yields without any side products were obtained under mild reaction conditions under sonication using a cheap catalyst i.e. SnCl 2 . Based on a simple nucleophilic displacement scheme, another set of 2-aminopyrimidines (83-87) was also synthesized. The second strategy involved modification of different functionalities of DHPM nucleus synthesized previously through one pot strategy. This led to introduction of different diversity elements farther at C5 and C6 positions leading to pyrimidines 88-92. Besides synthesizing a variety of pyrimidines, partial synthesis of ispinesib (a well known KSP inhibitor) was carried out via two routes with a view to optimize the reaction conditions and yield of the rate limiting step each of the two synthetic strategies. Since the synthesized dihydropyrimidines are anticipated to have important pharmacological properties, therefore, all these compounds were subjected to in vitro screening for studying their potential as urease inhibitors, xanthine oxidase inhibitors, thymidine phosphorylase inhibitors, potato disc tumor inhibitors and as antiglycation agents. Compound 53 was found to have very strong potential as urease inhibitor and may serve as a lead for developing into antiulcer drug. iiiIn silico studies were also carried out on the most active compounds identified in different bioassays by doing molecular docking and pharmacophore matching. Furthermore, in silico designing of DHPM based KSP, urease and thymidine phosphorylase inhibitors was carried out with a view to develop novel KSP, urease and TP inhibitors.