Some novel 2,3-dioxo-5-(substituted)arylpyrroles have been synthesized. Among these, pyrrolidine compound 1b was converted to 2,3-dioxo-5-aryl pyrrolidine 2b. Finally a set of hydrazone derivatives was obtained from the reaction of 2b with various hydrazine salts. The structures of all the new synthesized compounds were confirmed by elemental analyses, IR and 1H-NMR spectra.

A brief and efficient approach for the synthesis of (±)‐5‐benzyl‐4‐hydroxy‐2‐pyrrolidine (1) from phenylalanine racemate is described. The key step is the stereocontrolled reduction of the keto functionality of benzylated pyrrolidinone intermediate (6) via sodium borohydride in carboxylic acid medium furnishing both (R,R)‐ and (S,S)‐configured diastereomers. The natural (R,R) enantiomer (2), however, crystallized out from its racemic mixture. Structure of 2 was confirmed by NMR, IR, elemental analyzer, and single crystal X‐ray crystallographic techniques.

28 new pyrrolidine types of compounds as analogues for natural polyhydroxy alkaloids of codonopsinine were evaluated for their anti-MRSA activity using MIC and MBC value determination assay against a panel of S. aureus isolates. One pyrrolidine compound, MFM 501, exhibited good inhibitory activity with MIC value of 15.6 to 31.3 μg/mL against 55 S. aureus isolates (43 MRSA and 12 MSSA isolates). The active compound also displayed MBC values between 250 and 500 μg/mL against 58 S. aureus isolates (45 MRSA and 13 MSSA isolates) implying that MFM 501 has a bacteriostatic rather than bactericidal effect against both MRSA and MSSA isolates. In addition, MFM 501 showed no apparent cytotoxicity activity towards three normal cell lines (WRL-68, Vero, and 3T3) with IC50 values of >625 µg/mL. Selectivity index (SI) of MFM 501 gave a value of >10 suggesting that MFM 501 is significant and suitable for further in vivo investigations. These results suggested that synthetically derived intermediate compounds based on natural products may play an important role in the discovery of new anti-infective agents against MRSA.

Widespread resistance of Plasmodium falciparum to current artemisinin-based combination therapies necessitate the discovery of new medicines. Pharmacophoric hybridization has become an alternative for drug resistance that lowers the risk of drug–drug adverse interactions. In this study, we synthesized a new series of hybrids by covalently linking the scaffolds of pyrano[2,3-c]pyrazole with 4-aminoquinoline via an ethyl linker. All synthesized hybrid molecules were evaluated through in vitro screenings against chloroquine-resistant (K1) and -sensitive (3D7) P. falciparum strains, respectively. Data from in vitro assessments showed that hybrid 4b displayed significant antiplasmodial activities against the 3D7 strain (EC50 = 0.0130 ± 0.0002 μM) and the K1 strain (EC50 = 0.02 ± 0.01 μM), with low cytotoxic effect against Vero mammalian cells. The high selectivity index value on the 3D7 strain (SI > 1000) and the K1 strain (SI > 800) and the low resistance index value from compound 4b suggested that the pharmacological effects of this compound were due to selective inhibition on the 3D7 and K1 strains. Molecular docking analysis also showed that 4b recorded the highest binding energy on P. falciparum lactate dehydrogenase. Thus, P. falciparum lactate dehydrogenase is considered a potential molecular target for the synthesized compound.

Background Inflammation is known to involve in many pathological processes of different diseases, but the current therapy causes adverse effects. Thus, there is a great interest for the discovery of flavonoids as a valuable alternative to classical analgesic and anti-inflammatory agent with dual-inhibitory action, especially on both COX-2 and 5-LOX which can minimize or overcome this problem. Results In the present work, drug-likeness properties of the synthesized flavonoids via Lipinski’s Rule of Five were predicted using QikProp prior to evaluation of their COX and LOX inhibitory activities using enzyme assays. Subsequently, molecular docking was performed using GLIDE to analyse their binding behaviour. The results showed that all compounds obeyed the Lipinski’s Rule of Five. NPC6 and NPC7 had displayed better selectivity towards COX-2 as compared to Indomethacin with less than 50% inhibition against COX-1. In addition, these compounds also inhibited activity of 5-LOX. Their selectivity to COX-2 was due to the binding to hydrophobic region and extends to lobby region near the entrance of COX binding site forming hydrogen bond with Ser530. Interestingly, these compounds showed a similar binding mode as Zileuton in the active site of 5-LOX and formed hydrogen bond interaction with Ala424. Conclusion NPC6 and NPC7 had potential as dual inhibitor of COX-2 and 5-LOX. The scaffolds of these chemical entities are useful to be as lead compounds for the dual inhibition of COX-2 and 5-LOX.