Exploring Therapeutic Potential of 1,3,4-Oxadiazole Nucleus as Anticancer Agents: A Mini-review.

Cancer is an uncontrolled, abnormal growth of cells and the second cause of death after cardiovascular disease. At present, chemotherapy and related drugs have three major categories. All three have characteristic action and toxicity levels of antitumor activity. Due to indications of unwanted side effects, the exploration of novel and selective anticancer agents is crucially required. Heterocyclic compounds have always played a major role in research for new drug discovery and development. 1,3,4-oxadiazole derivatives are heterocyclic isomers having pharmacological properties and play an important role as antiproliferative agents. The present review summarizes anticancer activities of 1,3,4-oxadiazole derivatives against different cell lines, such as HCT-116, MCF-7, HeLa, SMMC-7721, and A549. The results showed that 1,3,4-oxadiazole and its derivatives have the potential to play a major role as an anticancer agent with fewer side effects.

2-Substituted Benzoxazoles as Potent Anti-Inflammatory Agents: Synthesis, Molecular Docking and In vivo Anti-Ulcerogenic Studies.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are the commonly used therapeutic interventions of inflammation and pain that competitively inhibit the cyclooxygenase (COX) enzymes. Several side effects like gastrointestinal and renal toxicities are associated with the use of these drugs. The therapeutic anti-inflammatory benefits of NSAIDs are produced by the inhibition of COX-2 enzymes, while undesirable side effects arise from the inhibition of COX-1 enzymes. OBJECTIVE: In the present study, a new series of 2-substituted benzoxazole derivatives 2(a-f) and 3(ae) were synthesized in our lab as potent anti-inflammatory agents with outstanding gastro-protective potential. The new analogs 2(a-f) and 3(a-e) were designed depending upon the literature review to serve as ligands for the development of selective COX-2 inhibitors. METHODS: The synthesized analogs were characterized using different spectroscopic techniques (FTIR, 1HNMR, 13CNMR) and elemental analysis. All synthesized compounds were screened for their binding potential in the protein pocket of COX-2 and evaluated for their anti-inflammatory potential in animals using the carrageenan-induced paw edema method. Further 5 compounds were selected to assess the in vivo anti-ulcerogenic activity in an ethanol-induced anti-ulcer rat model. RESULTS: Five compounds (2a, 2b, 3a, 3b and 3c) exhibited potent anti-inflammatory activity and significant binding potential in the COX-2 protein pocket. Similarly, these five compounds demonstrated a significant gastro-protective effect (**p<0.01) in comparison to the standard drug, Omeprazole. CONCLUSION: Depending upon our results, we hypothesize that 2-substituted benzoxazole derivatives have excellent potential to serve as candidates for the development of selective anti-inflammatory agents (COX-2 inhibitors). However, further assessments are required to delineate their underlying mechanisms.

Isatin-hydrazide conjugates as potent α-amylase and α-glucosidase inhibitors: Synthesis, structure and invitro evaluations.

Managing diabetes that is a global life-threatening problem, remains a challenge for the scientific community. The inhibition of α-amylase and α-glucosidase enzymes which are responsible for the digestion of dietary carbohydrates is an effective strategy to control postprandial hyperglycemia. Herein, we report the novel and highly potent inhibitors of α-amylase and α-glucosidase, namely isatin-hydrazide conjugates 1a - 1j that are easily accessed in two steps from simple and inexpensive commercially available isatin. The in vitro bio-evaluations of these compounds revealed that conjugates 1a, 1h and 1f are highly potent inhibitors of α-amylase with IC50 values of 19.6, 12.1 and 18.3 µg/ml, respectively as compared to the standard, acarbose (IC50 = 36.2 µg/ml). Similarly, the conjugates 1a, 1b, 1d, 1f and 1i showed significant activity against α-glucosidase with IC50 values of 14.8, 25.6, 13.2, 14.5 and 16.5 µg/ml, respectively as compared to the acarbose (IC50 = 34.5 µg/ml). Notably, the compounds 1a and 1f were found to be highly potent against both α-amylase and α-glucosidase enzymes, demonstrating about two-fold better inhibitory activity than the reference inhibitor. Molecular docking studies were performed to recognize the possible binding modes of the compounds with the active pocket of the enzymes. The results of this study divulge the potential of these compounds as powerful and inexpensive lead molecules for future investigations.