Structure Activity Relationship of Key Heterocyclic Anti-Angiogenic Leads of Promising Potential in the Fight against Cancer

Abstract

Pathological angiogenesis is a hallmark of cancer; accordingly, a number of anticancer FDA-approved drugs act by inhibiting angiogenesis via different mechanisms. However, the development process of the most potent anti-angiogenics has met various hurdles including redundancy, multiplicity, and development of compensatory mechanisms by which blood vessels are remodeled. Moreover, identification of broad-spectrum anti-angiogenesis targets is proved to be required to enhance the efficacy of the anti-angiogenesis drugs. In this perspective, a proper understanding of the structure activity relationship (SAR) of the recent anti-angiogenics is required. Various anti-angiogenic classes have been developed over the years; among them, the heterocyclic organic compounds come to the fore as the most promising, with several drugs approved by the FDA. In this review, we discuss the structure–activity relationship of some promising potent heterocyclic anti-angiogenic leads. For each lead, a molecular modelling was also carried out in order to correlate its SAR and specificity to the active site. Furthermore, an in silico pharmacokinetics study for some representative leads was presented. Summarizing, new insights for further improvement for each lead have been reviewed.

The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer

“…Overexpression of various types of RTKs is found in different types of cancer, which encouraged medicinal chemists worldwide to develop numerous RTKs inhibitors [ 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 ]. Among these efforts, several DDR kinase inhibitors have been discovered so far, some of them have been demonstrated to possess a promising therapeutic potential.…”

Perspective for Discovery of Small Molecule IL-6 Inhibitors through Study of Structure–Activity Relationships and Molecular Docking

“…Study of the structure–activity relationships (SARs) of previously designed and synthesized compounds is paramount in developing more potent drugs. , To predict SARs for a specific series of compounds, there must be enough derivatives with reported biological activity. To date, the only confirmed targeted therapy for IL-6 inhibition is the inhibition of the gp130 extracellular D1 domain.…”

New horizons in drug discovery of lymphocyte-specific protein tyrosine kinase (Lck) inhibitors: a decade review (2011–2021) focussing on structure–activity relationship (SAR) and docking insights

“…Several kinases were found to be associated with different human disorders including cancer initiation and progression. Also, the recent medicinal chemistry research targeting development of small molecule kinase inhibitors for the treatment of various diseases including cancer has been proven to be a successful strategy [33][34][35][36][37][38][39][40][41][42][43][44][45][46] . Among these cancer-related kinases, Lck was reported to be the promotor of BCR signals in chronic lymphocytic leukaemia (CLL) via catalysis of the proximal phosphorylation of CD79a and the induction of distal signalling events involving phosphorylation of Syk, activation of MAPK, NF-kB, ERK, and PI3K/ Akt signalling pathways that are responsible for CLL cell survival following BCR cross-linking.…”