Flexible duplex is proposed to adapt to the channel and traffic asymmetry for future wireless networks. In this paper, we propose two novel algorithms within the flexible duplex framework for joint uplink and downlink resource allocation in multi-cell scenario, named SAFP and RMDI, based on the awareness of interference coupling among wireless links. Numerical results show significant performance gain over the baseline system with fixed uplink/downlink resource configuration, and over the dynamic TDD scheme that independently adapts the configuration to time-varying traffic volume in each cell. The proposed algorithms achieve two-fold increase when compared with the baseline scheme, measured by the worst-case quality of service satisfaction level, under a low level of traffic asymmetry. The gain is more significant when the traffic is highly asymmetric, as it achieves three-fold increase.