Ram Awatar Maurya

Pyranocoumarins: A new class of anti-hyperglycemic and anti-dyslipidemic agents

A series of pyranocoumarin derivatives were synthesized and evaluated in vivo for their anti-hyperglycemic as well as anti-dyslipidemic activities. Compounds 7a, 7c, 8a, 8b, 8c, 8e and 8f have shown promising anti-hyperglycemic activities in sucrose loaded model (SLM) as well as sucrose challenged streptozotocin induced diabetic rat model (STZ). Compounds 8a and 8b were showing 38.0% and 42.0% blood glucose lowering activity in db/db mice model. In vitro anti-hyperglycemic activity evaluation exhibited that compounds 8a (IC(50)=24.5 microM) and 8b (IC(50)=36.2 microM) are potential PTP-1B inhibitors thereby revealing their possible mechanism of anti-diabetic action. Compounds 7a, 7b, 8a, 8b, 8d, 8e and 8f have shown significant anti-dyslipidemic activity in triton induced dyslipidemia in rats.

Design and synthesis of 2,4-disubstituted polyhydroquinolines as prospective antihyperglycemic and lipid modulating agents.

A series of 2,4-disubstituted polyhydroquinoline were synthesized and evaluated for their in vivo antihyperglycemic as well as antidyslipidemic activities. Several synthesized compounds have exhibited promising in vivo antihyperglycemic in SLM, STZ-S, and db/db mice model along with significant lipid and TG modulating activity. All these compounds were evaluated in various in vitro models of diabetes to know the possible mechanism of their antihyperglycemic action. Interestingly, compounds 3a-r (diaryl substitution) have exhibited promising protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity whereas, compounds 5a-d (acid substituted) have shown significant glycogen phosphorylase activity.

Synthesis and biological evaluation of N-aryl-1,4-dihydropyridines as novel antidyslipidemic and antioxidant agents.

N-aryl-1,4-dihydropyridines 2a-n were synthesized via iodine catalyzed three-component reaction of cinnamaldehydes, anilines and 2-keto esters in methanol. The synthesized compounds were screened for their antidyslipidemic and antioxidant activity in vivo and in vitro. Compounds 2a, 2g, and 2l have exhibited promising lipid and TG lowering activity, whereas compounds 2m and 2n have showed potent antioxidant activity.

Novel 2-aryl-naphtho[1,2-d]oxazole derivatives as potential PTP-1B inhibitors showing antihyperglycemic activities.

A series of 2-aryl-naphtho[1,2-d]oxazole derivatives have been synthesized and evaluated for PTP-1B inhibitory activity. The compounds have been screened in vivo for antidiabetic activity under sucrose loaded model (SLM), sucrose-challenged streptozotocin-induced diabetic rat model (STZ-S) and db/db mice model. Compounds 8 and 12 have shown promising PTP-1B inhibitory activity, significant antidiabetic activity, moderate lipid and triglyceride lowering activity.

Design and synthesis of 3,5-diarylisoxazole derivatives as novel class of anti-hyperglycemic and lipid lowering agents

We have designed 1,3-disubstituted-5-membered heteroaromatic ring system as a common core motif from known anti-hyperglycemic agents. Designed compounds were synthesized and screened for in vivo anti-hyperglycemic activity in sucrose loaded model (SLM), sucrose-challenged streptozotocin-induced diabetic rat model (STZ-S) as well as db/db mice model. Some of the synthesized compounds showed promising in vivo anti-hyperglycemic as well as moderate lipid lowering activity. Synthesized Compounds were screened in various in vitro models of type-2 diabeties such as DPP-4, PTP1B and PPARgamma to know the mechanism of their anti-hyperglycemic action. None of the synthesized compounds showed DPP-4 inhibitory as well as PPARgamma activity. These compounds have shown promising PTP-1B inhibitory activity there by revealing that compounds exhibit anti-diabetic activity by PTP1B pathway.

Diversity-oriented synthesis of benzimidazole, benzoxazole, benzothiazole and quinazolin-4(3H)-one libraries via potassium persulfate–CuSO4-mediated oxidative coupling reactions of aldehydes in aqueous micelles

Libraries of 2-substituted-benzimidazoles, benzoxazoles, benzothiazoles as well as quinazolin-4(3H)-ones were synthesized via potassium persulfate–CuSO4-mediated oxidative coupling of aldehydes with o-phenylenediamines, o-aminophenols, o-aminothiophenols, and anthranilamide, respectively, in aqueous micelles. The strategy opens a way for rapid generation of libraries of small heterocycles for biological screening. The reagent is commercially available, cheap, and highly chemoselective. The yields were superior in aqueous micelles to those in organic solvents. Short reaction times, large-scale synthesis, excellent chemoselectivity, excellent yields, as well as environmental friendliness are the main advantages of this diversity-oriented synthesis.

Oxidative aromatization of 1,4-dihydropyridines and pyrazolines using HbA–H2O2: An efficient biomimetic catalyst system providing metabolites of drug candidates

Human hemoglobin (HbA) efficiently catalyses the oxidative aromatization of 1,4-dihydropyridines (1,4-DHPs) and pyrazolines with hydrogen peroxide in phosphate buffer. The results of the study reveal that the rates of oxidative aromatization of 1,4-DHPs are substituent dependent. Thus, the present study is very useful in understanding the metabolism of 1,4-DHP drugs in liver by cytochrome P450 and designing novel drugs as well as modifying the existing drugs for better pharmacokinetic profile.