المحكم والمتشابه وموقف المفسر منهما

The Mohkam and Mutashabeh is a renowned terminology of the Quranic Sciences and commentators of the Holy Quran described it in details, according to root words of Mohkam, it means Stopping and perfecting the things, this basic meaning can be seen in all the types and variations of this word. On the other hand we have the word Mutashabeh which root meaning is complication and unclearness. If we discuss both of the words as a terminology of the Quranic sciences, we can define Mohkam as “one which define itself without any other thing” or “one which has no need to be defined by something else” and Mutashabeh is “one which can’t define itself and need to be explained by someone else”. We will move on to discuss both terms in Holy Quran as a terminology to describe its multiple variations in the Holy Quran, its types and further we will discuss that why the Holy Quran contains both terms, in other words, we can say which are the logics and reasons of including Mutashabeh verses in the Holy Quran. In addition, we will mention the point of views of various renowned commentators and fields experts which give us a clear and sound concept about both of the terms.

Syntheses of Pyridine and Pyrimidine Derivatives in Search of Potential Therapeutic Agents

This research work consists of the syntheses of pyridine and pyrimidine derivatives by adopting various synthetic chemical transformations and screening of their biological activities. All compounds were fully characterized by various spectroscopic techniques such as 1H-NMR, 13C-NMR, EI-MS and HREI-MS. Melting points of all compounds were also recorded. This dissertation consists of two chapters based on the extensive literature and research findings regarding the three libraries of synthetic compounds. Each chapter has its own compounds numbering, tables, figures, schemes and references. Chapter-1 has been subdivided into two parts (part A and B). Part A composed of the broad literature survey regarding the general introduction of pyridine, its biological background and various synthetic protocols. In addition, it also deals with the rationale behind the current study. Fifty-seven synthesized derivatives of pyridine (21-77) were evaluated for their in vitro activities. all derivatives showed more potent inhibition against α-glucosidase in vitro, however, compounds 29, 35, 43, 44, 49, 56, 61, 70, and 75 showed more than hundred-fold better activity than standard acarbose (IC50 = 856.45 ± 5.60 μM). Out of fifty-seven derivatives, only four compounds 28, 30, 42, and 43 showed weak in vitro dipeptidyl peptidase inhibitory activity as compared to standard sitagliptin (IC50 = 0.0246 ± 0.004 µM). Remaining compounds were found to be completely inactive. Compound 38 showed potent antileishmanial activity while compound 22, 39, 40, 41, 46, 49, 55, and 67 showed weak to significant antileishmanial activities when compared with the standards amphotericin B (IC50 = 0.29 ± 0.05 µM) and pentamidine (IC50 = 5.09 ± 0.04 µM). Ten analogs 22, 25, 35, 38, 42, 46, 49, 63, 70, and 75 manifested themselves to be more potent while ten anlogs 31, 33, 36, 37, 39, 41, 45, 57, 73, and 74 showed weak to moderate activity in comparison with standard ibuprofen (IC50 = 11.2 ± 1.9 µM). Four analogs 25, 28, 35, and 49 were attributed to be significantly active while 43 showed moderate activity in comparison with standard rutin. Only compound 64 was observed to be the most potent against tyrosinase enzyme while, derivative 21, 38, and 50 showed moderate to weak tyrosinase inhibitory activity. In Part-B further pyridine derivatives 78-118 were synthesized and screened to check their in vitro biological activities. In vitro β-glucuronidase inhibition of all synthetic derivatives 78-118 were checked which showed that out of forty-one derivatives, twentyeight derivatives were showed more potency as compared to the standard D-saccharic acid 1,4-lactone (IC50 = 48.40 ± 0.25 μM). Among which compound 103 (IC50 = 1.10 ± 0.10 μM) was the most potent compound while compounds 102, 89, 116, 96, 110, and 111 were also the potent about ten to twenty fold better than standard. These derivatives were also evaluated for their urease inhibitory activity. Compound 78, 88, 92, 106, and 116 showed good to moderate potential against urease as compared with the standard thiourea, while remaining derivatives were found to be non-active. Ten Compounds 78, 80, 87, 90, 96, 97, 104, 106, 111, and 115 were showed more antiinflammatory potency than the standard ibuprofen. Out of 98 synthesized derivatives of pyridine, 29 compounds 25, 28, 31, 34, 43, 45, 48, 49, 55, 57, 58, 60, 61, 69, 71, 72, 74, 75, 83, 89, 97, 98, 102, 103, 109, 110, 111, 112, and 116 were new compounds. Chapter 2 describes introduction of pyrimidine, its biological background and various synthetic protocols. In addition, it also deals with the rationale behind the current study. One pot three-component synthesis was adopted to synthesized Dihydropyrimidone derivatives (150-189) and screened for in vitro biological evaluation. Forty synthetic derivatives of dihydropyrimidones were screened for antiinflammatory activity. Six derivatives 151, 157, 160, 162, 166, and 182 were found to be active and showed more significant to less significant activity in the comparison of standard ibuprofen. All of these derivatives were found to be inactive in intiglycation assay and against tyrosinase enzyme. All derivatives were also screened for their in vitro β-glucuronidase inhibitory activity. Among forty analogs, eighteen compounds 157-159, 162-166, 171-178, 181, and 182 were possess more inhibitory potential than the standard D-saccharic acid 1,4lactone (IC50 = 48.4 ± 1.25 μM). In DPPH activity, only one compound 162 is active which is two-fold more potent than the standards BHT (IC50 = 128.2 ± 0.5 µM) and remaining compounds were found to be inactive.