Burn patients have the highest metabolic rate among critically ill or injured patients. Because propranolol decreases energy expenditure and muscle protein catabolism, in this study, we hypothesized that propranolol would improve healing process and decrease wound-healing time. This study was a double-blind randomized clinical trial; a total of 79 burn patients who referred to this center from January 2006 to January 2007 fulfilled the inclusion criteria. Thirty-seven patients were randomly placed in propranolol group and 42 in control group. The propranolol group received propranolol orally with the dose of 1 mg/kg/d and maximum dose of 1.98 mg/kg/d given in six divided doses. This dose was adjusted to decrease the resting heart rate by 20% from each patient's baseline value. The control group received placebo. The most common cause of burn in both groups was flame followed by flash. Patients with superficial burns in the propranolol group needed less time to heal for acceptable wound healing in superficial burns (16.13+/-7.40 days vs 21.52+/-7.94 days; P=.004). We also found that patients with deep burn injury needed less time to be ready for skin graft (28.23+/-8.43 days vs 33.46+/-9.17 days; P=.007) when compared to that of the control group. The use of propranolol decreased the size of the burn wound that finally needed skin graft. Patients in the propranolol group with an average burn size of 31.42% TBSA finally needed 13.75% of TBSA skin graft compared with that of control patients with an average burn size of 33.61% TBSA who needed 18.72% of TBSA skin graft, and patients in the control group with an average burn size of 33.61% TBSA finally needed 18.72% of TBSA skin graft (P=.006). Patients in the propranolol group had a shorter hospital stay period than the control group (30.95+/-8.44 days vs 24.41+/-8.11 days; P=.05). Administration of propranolol, improved burn wound healing, and decreased healing time and hospital stay period. The use of propranolol decreased the surface area of wounds that needed to be skin grafted.

Isatin is an important compound from the biological aspect of view. It is an endogenous substance and moreover; various pharmacological activities have been reported for isatin and its derivatives. In-vitro cytotoxic effects of the prepared isatin Schiff bases toward HeLa, LS180 and Raji human cancer cell lines has been reported in our previous work. 3-(2-(4-nitrophenyl)hydrazono) indolin-2-one was found to be the most potent one among the studied compounds (IC(30) =12.2 and 21.8 μM in HeLa and LS-180 cell lines, respectively). Obtained biological data could be well interpreted using docking binding energies toward vascular endothelial growth factor receptor (VEGFR-2); a key anticancer target being biologically investigated against various isatin derivatives. In the present work, quantum mechanical (QM) method including functional B3LYP in association with split valence basis set using polarization functions (Def2-SVP) was used to estimate individual ligand-residue interaction energies for the docked 3-(2-(4-nitrophenyl)hydrazono) indolin-2-one into VEGFR-2 active site. Results were further interpreted via calculated polarization effects induced by individual amino acids of the receptor active site. A fairly good correlation could be found between polarization effects and estimated binding energies (R(2) =0.7227). Conformational analysis revealed that 3-(2-(4-nitrophenyl) hydrazono) indolin-2-one might not necessarily interact with the VEGFR-2 active site in its minimum energy conformation.

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An effective one-pot synthesis of bis(dihydropyrimidinonoe)benzenes using chlorotrimethylsilane (TMSCl) through Biginelli condensation reaction of terephthalic aldehyde, 1,3-dicarbonyl compounds and (thio)urea or guanidine under microwave irradiation conditions is described. Excellent yields of the products and simple work-up are attractive features of this green protocol. Then, the cytotoxic activities of these compounds were evaluated on five different human cancerous cell lines (Raji, HeLa, LS-180, SKOV-3 and MCF7). Their cytotoxic study indicated that they possessed a weak to moderate activity. Furthermore, the higher activity of compound 4b bearing sulfur in C 2 position of pyrimidinone ring showed the importance of this site for cytotoxic activity of these compounds.Key words: Biginelli reaction, cytotoxicity, dihyropyrimidinone, microwave irradiation, multicomponent, terephthalic aldehyde, TMSCl Multicomponent reactions (MCRs) can be distinguished from classical, sequential two-component chemistry synthesis processes in that they use three or more chemical starting materials as the input for product formation. Up to seven starting components have been used, and MCRs have often been shown to produce higher product yields than classical chemistry (1-3).Multicomponent reactions are finding increasing use in the discovery process of new drugs and agrochemicals (4-6) and offer significant advantages over conventional linear-type syntheses. MCR condensations involve three or more compounds reacting in a single one-pot reaction, but consecutively to form a new product, which contains the essential parts of all the starting materials. The search and discovery for new MCR's on one hand (7), and the full exploitation of already known multicomponent reactions on the other hand, is therefore of considerable current interest. One such MCR that belongs in the latter category is the venerable Biginelli dihydropyrimidine synthesis. A few years ago, Pietro Biginelli reported on the one-pot cyclocondensation reaction of an aldehyde, a b-ketoester, and urea (or thiourea), a procedure known as the Biginelli reaction, is receiving increased attention. More than a century ago, Biginelli intuitively anticipated the synthetic potential of multicomponent reactions by combining in a single flask the reactants of two different reactions having one component in common (8). The result of the three-component reaction was a new product that was correctly characterized as a substituted 3,4-dihydropyrimidine-2(1H)-one (DHPM).3,4-Dihydropyrimidinones (DHPMs) constitute a very important class of organic compounds because of their attractive pharmacological properties, including antiviral, antitumour, antibacterial activities [For a review, see (9); references cited therein (10)].